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1. Kanazawa I, Yamaguchi T, Yamane Y, Murakami N, Kato Y, Sugimoto T: Acromegaly associated with monoclonal gammopathy of undetermined significance (MGUS). Endocr J; 2006 Oct;53(5):687-91
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  • [Title] Acromegaly associated with monoclonal gammopathy of undetermined significance (MGUS).
  • Here we report the case of a 65-year-old woman with acromegaly complicated with monoclonal gammopathy of undetermined significance (MGUS).
  • The patient visited Shimane University Hospital for treatment of spinal canal stenosis, and was diagnosed as acromegaly with GH 43.1 ng/ml, insulin-like growth factor (IGF)-I 510 ng/ml and the detection of a pituitary adenoma by MRI.
  • She was also diagnosed as MGUS with IgG 2208 mg/dl, the existence of IgG-kappa type monoclonal protein, and 5.6% plasma cells in bone marrow.
  • We suspect a pathogenetic link between acromegaly and MGUS in this case, because both GH and IGF-I are known to directly promote immunoglobulin production from plasma cells, thus inducing the proliferation of the cells in vitro.
  • [MeSH-major] Acromegaly / complications. Monoclonal Gammopathy of Undetermined Significance / complications

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  • (PMID = 16926522.001).
  • [ISSN] 0918-8959
  • [Journal-full-title] Endocrine journal
  • [ISO-abbreviation] Endocr. J.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Immunoglobulin G; 12629-01-5 / Human Growth Hormone; 67763-96-6 / Insulin-Like Growth Factor I
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2. Sackmann F, Pavlovsky MA, Corrado C, Pizzolato M, Alejandre M, Pavlovsky S: Prognostic factors in monoclonal gammopathy of undetermined significance. Haematologica; 2008 Jan;93(1):153-4

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Prognostic factors in monoclonal gammopathy of undetermined significance.
  • A retrospective evaluation of 285 patients with monoclonal gammopathy of undetermined significance was performed to identify variables associated with progression, actuarial progression free survival (PFS) and overall survival (OS).
  • Three variables, level of uninvolved immunoglobulins (HR 4.98, CI95% 2 -12.4, p=0.0006), monoclonal protein concentration (HR 4.04, CI95% 1.6-10.34, p=0.004), and erythrosedimentation rate (HR 3.94, CI95% 1.33-11.6, p=0.01), showed independent prognostic significance.
  • [MeSH-major] Monoclonal Gammopathy of Undetermined Significance / diagnosis. Monoclonal Gammopathy of Undetermined Significance / therapy
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Disease Progression. Disease-Free Survival. Female. Humans. Immunoglobulins / metabolism. Male. Middle Aged. Prognosis. Retrospective Studies. Time Factors. Treatment Outcome

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  • [CommentIn] Haematologica. 2008 Mar;93(3):e38 [18310534.001]
  • (PMID = 18166806.001).
  • [ISSN] 1592-8721
  • [Journal-full-title] Haematologica
  • [ISO-abbreviation] Haematologica
  • [Language] eng
  • [Publication-type] Letter
  • [Publication-country] Italy
  • [Chemical-registry-number] 0 / Immunoglobulins
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3. Wu WC, Chen SC, Hsieh JT, Chen J, Chang HC: Penile tuberculosis associated with monoclonal gammopathy of undetermined significance. J Formos Med Assoc; 2006 Sep;105(9):753-5
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  • [Title] Penile tuberculosis associated with monoclonal gammopathy of undetermined significance.
  • Monoclonal gammopathy of undetermined significance was diagnosed after serum and urine electrophoresis studies, and repeated bone marrow studies.
  • Although rare, the possibility of TB as a cause of genital ulcer should be kept in mind.

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  • (PMID = 16959623.001).
  • [ISSN] 0929-6646
  • [Journal-full-title] Journal of the Formosan Medical Association = Taiwan yi zhi
  • [ISO-abbreviation] J. Formos. Med. Assoc.
  • [Language] ENG
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Singapore
  • [Chemical-registry-number] 0 / Antitubercular Agents; 2KNI5N06TI / Pyrazinamide; 8G167061QZ / Ethambutol; V83O1VOZ8L / Isoniazid; VJT6J7R4TR / Rifampin
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4. Chim CS, Liang R, Leung MH, Kwong YL: Aberrant gene methylation implicated in the progression of monoclonal gammopathy of undetermined significance to multiple myeloma. J Clin Pathol; 2007 Jan;60(1):104-6
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Aberrant gene methylation implicated in the progression of monoclonal gammopathy of undetermined significance to multiple myeloma.
  • Malignant transformation is a multistep process that may involve dysregulation of oncogenes and tumour suppressor genes, and monoclonal gammopathy of undetermined significance (MGUS) is believed to be a precursor of multiple myeloma.
  • To investigate whether aberrant promoter methylation might be involved in the evolution of MGUS to multiple myeloma, we examined the p16, protein tyrosine phosphatase, non-receptor type 6 (SHP1), death-associated protein (DAP) kinase, E-cadherin and oestrogen receptor genes, most being tumour suppressor genes, by methylation-specific polymerase chain reaction.
  • In 32 cases of multiple myeloma and 19 cases of MGUS, significantly more frequent methylation of p16 (p = 0.001), SHP1 (p< or =0.001) and E-cadherin (p< or =0.001) genes was found in multiple myeloma than in MGUS.
  • Methylation of DAP kinase and oestrogen receptor genes was comparable in multiple myeloma and MGUS.
  • In conclusion, methylation of p16, SHP1 and E-cadherin genes might be involved in the progression of MGUS to multiple myeloma.
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. DNA, Neoplasm / genetics. Disease Progression. Female. Genes, Tumor Suppressor. Humans. Male. Middle Aged. Multiple Myeloma / genetics. Neoplasm Proteins / genetics. Polymerase Chain Reaction / methods. Promoter Regions, Genetic / genetics

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  • (PMID = 17213358.001).
  • [ISSN] 0021-9746
  • [Journal-full-title] Journal of clinical pathology
  • [ISO-abbreviation] J. Clin. Pathol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / DNA, Neoplasm; 0 / Neoplasm Proteins
  • [Other-IDs] NLM/ PMC1860599
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5. Lozeron P, Adams D: Monoclonal gammopathy and neuropathy. Curr Opin Neurol; 2007 Oct;20(5):536-41
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  • [Title] Monoclonal gammopathy and neuropathy.
  • PURPOSE OF REVIEW: To provide clinically useful guidelines in the management of neuropathy associated with monoclonal gammopathy from a review of the most recent literature and our own experience.
  • RECENT FINDINGS: Recent data on neuropathy associated with monoclonal gammopathy come from better descriptions of subgroups, and from new treatment compounds that have shown encouraging results in different entities.
  • SUMMARY: Neuropathies associated with monoclonal gammopathy are relatively rare and most often the neuropathy reveals the monoclonal gammopathy.
  • The main described subgroup is IgM anti-(myelin-associated glycoprotein) neuropathy, which presents as a relatively benign, slowly progressive sensory neuropathy.
  • Neuropathies associated with monoclonal gammopathy have various neurological and general outcomes, including life-threatening entities such as light-chain amyloid neuropathy and POEMS syndrome.
  • Treatment choice is wide and depends both on the underlying haematological disorder and severity of the neuropathy.
  • Intravenous immunoglobulin should be assessed in demyelinating monoclonal gammopathy of undetermined significance neuropathy.
  • The possibility of a malignant evolution of monoclonal gammopathy of undetermined significance warrants regular haematological monitoring.
  • [MeSH-major] Paraproteinemias / diagnosis. Paraproteinemias / immunology. Peripheral Nerves / immunology. Peripheral Nervous System Diseases / diagnosis. Peripheral Nervous System Diseases / immunology

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  • (PMID = 17885441.001).
  • [ISSN] 1350-7540
  • [Journal-full-title] Current opinion in neurology
  • [ISO-abbreviation] Curr. Opin. Neurol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Number-of-references] 56
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6. Cheung WI, Leung VK, Luk IS, Loke TK, Chan JC, Chau TN: Splenic tuberculosis associated with monoclonal gammopathy of undetermined significance and pericarditis. Hong Kong Med J; 2009 Aug;15(4):291-3
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  • [Title] Splenic tuberculosis associated with monoclonal gammopathy of undetermined significance and pericarditis.
  • Tuberculosis usually affects the respiratory system, but it may present atypically involving multiple systems, extrapulmonary systems, and manifest as a protein disorder.
  • Here we report a case of splenic tuberculosis associated with monoclonal gammopathy of undetermined significance, and pericarditis.
  • The diagnosis, confirmed by a plugged biopsy of the spleen, precluded the need for splenectomy in this patient and allowed prompt initiation of treatment, thereby avoiding the complications of tuberculous pericarditis and splenic infection.

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  • (PMID = 19652238.001).
  • [ISSN] 1024-2708
  • [Journal-full-title] Hong Kong medical journal = Xianggang yi xue za zhi
  • [ISO-abbreviation] Hong Kong Med J
  • [Language] ENG
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] China
  • [Chemical-registry-number] 0 / Antitubercular Agents; 0 / Biomarkers
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7. Rajkumar SV: Prevention of progression in monoclonal gammopathy of undetermined significance. Clin Cancer Res; 2009 Sep 15;15(18):5606-8
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  • [Title] Prevention of progression in monoclonal gammopathy of undetermined significance.
  • Monoclonal gammopathy of undetermined significance (MGUS) is a common premalignant plasma cell proliferative disorder with a lifelong risk of progression to multiple myeloma.

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  • (PMID = 19737944.001).
  • [ISSN] 1078-0432
  • [Journal-full-title] Clinical cancer research : an official journal of the American Association for Cancer Research
  • [ISO-abbreviation] Clin. Cancer Res.
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / CA062242-140011; United States / NCI NIH HHS / CA / P01 CA062242-140011; United States / NCI NIH HHS / CA / CA107476-06; United States / NCI NIH HHS / CA / P01 CA062242; United States / NCI NIH HHS / CA / R01 CA107476-06; United States / NCI NIH HHS / CA / R01 CA107476; United States / NCI NIH HHS / CA / CA107476; United States / NCI NIH HHS / CA / CA62242
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] United States
  • [Other-IDs] NLM/ NIHMS140347; NLM/ PMC2759099
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8. Blotta S, Tassone P, Prabhala RH, Tagliaferri P, Cervi D, Amin S, Jakubikova J, Tai YT, Podar K, Mitsiades CS, Zullo A, Franco B, Anderson KC, Munshi NC: Identification of novel antigens with induced immune response in monoclonal gammopathy of undetermined significance. Blood; 2009 Oct 08;114(15):3276-84
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Identification of novel antigens with induced immune response in monoclonal gammopathy of undetermined significance.
  • The transformation from monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM) is thought to be associated with changes in immune processes.
  • We have therefore used serologic analysis of recombinant cDNA expression library to screen the sera of MGUS patients to identify tumor-associated antigens.
  • A total of 10 antigens were identified, with specific antibody responses in MGUS.
  • Importantly, the gene responsible for the oral-facial-digital type I syndrome (OFD1) had response in 6 of 29 (20.6%) MGUS patients but 0 of 11 newly diagnosed MM patients.
  • Interestingly, 3 of 11 (27.2%) MM patients after autologous stem cell transplantations showed responses to OFD1.
  • We have confirmed T-cell responses against OFD1 in MGUS and observed down-regulation of GLI1/PTCH1 and p-beta-catenin after OFD1 knock-down with specific siRNA, suggesting its functional role in the regulation of Hh and Wnt pathways.
  • These findings demonstrate OFD1 as an important immune target and highlight its possible role in signal transduction and tumorigenesis in MGUS and MM.
  • [MeSH-minor] Aged. Aged, 80 and over. Apoptosis Regulatory Proteins / genetics. Apoptosis Regulatory Proteins / immunology. Carrier Proteins / genetics. Carrier Proteins / immunology. DNA, Complementary / genetics. Female. Humans. Male. Nuclear Proteins / genetics. Nuclear Proteins / immunology. Patched Receptors. Patched-1 Receptor. RNA-Binding Proteins / genetics. RNA-Binding Proteins / immunology. Receptors, Cell Surface / genetics. Receptors, Cell Surface / immunology. Signal Transduction / immunology. Stem Cell Transplantation. T-Lymphocytes / immunology. Transplantation, Autologous. beta Catenin / genetics. beta Catenin / immunology

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  • (PMID = 19587378.001).
  • [ISSN] 1528-0020
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Grant] United States / PHS HHS / / P01-78378; Italy / Telethon / / TGM06Z08; United States / NCI NIH HHS / CA / P50CA-100707; United States / NCI NIH HHS / CA / P01 CA078378; United States / PHS HHS / / R01-129494; United States / NCI NIH HHS / CA / P01 CA155258; United States / NCI NIH HHS / CA / P50 CA100707
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Apoptosis Regulatory Proteins; 0 / Autoantigens; 0 / Carrier Proteins; 0 / DNA, Complementary; 0 / IRF2BP2 protein, human; 0 / Nuclear Proteins; 0 / OFD1 protein, human; 0 / PTCH protein, human; 0 / Patched Receptors; 0 / Patched-1 Receptor; 0 / Proteins; 0 / RNA-Binding Proteins; 0 / Receptors, Cell Surface; 0 / beta Catenin
  • [Other-IDs] NLM/ PMC2759650
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9. Ramchandren S, Lewis RA: Monoclonal gammopathy and neuropathy. Curr Opin Neurol; 2009 Oct;22(5):480-5
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Monoclonal gammopathy and neuropathy.
  • PURPOSE OF REVIEW: The management of peripheral neuropathy associated with monoclonal gammopathies has been advanced by recent clinical studies.
  • We review the causal association between monoclonal gammopathy and neuropathy, and critically review the recent evidence on treatment.
  • RECENT FINDINGS: IgM monoclonal gammopathy of undetermined significance (MGUS) is the most commonly found monoclonal gammopathy associated with neuropathy.
  • Neuropathies associated with specific lymphoproliferative disorders may not respond to treatments aimed at that disorder.
  • Standard immunomodulatory agents including steroids, intravenous immunoglobulin, and plasmapheresis have shown limited efficacy in IgM monoclonal gammopathy of undetermined significance.
  • Newer studies have shown promising results with rituximab, a monoclonal antibody which targets the B cell surface antigen CD20 and results in a rapid and sustained depletion of B cells.
  • SUMMARY: There is a clear association between peripheral neuropathy and IgM MGUS with characteristic clinical, electrophysiology and pathologic features that make the disorder distinct from chronic inflammatory demyelinating polyneuropathy.
  • The IgG and IgA monoclonal gammopathies are rarely associated with specific neuropathies.
  • Long-term studies looking at the association between specific immunologic markers and disease recurrence are needed to ultimately develop targeted therapies.

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  • (PMID = 19625962.001).
  • [ISSN] 1473-6551
  • [Journal-full-title] Current opinion in neurology
  • [ISO-abbreviation] Curr. Opin. Neurol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Number-of-references] 57
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10. Freytes CO: Emerging concepts in monoclonal gammopathy of undetermined significance. Bol Asoc Med P R; 2010 Oct-Dec;102(4):43-6
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Emerging concepts in monoclonal gammopathy of undetermined significance.
  • Monoclonal gammopathy of undetermined significance (MGUS) is frequently diagnosed in the elderly population.
  • This short review discusses basic concepts and recent developments that will facilitate the diagnosis and management of this condition by primary care physicians and specialists in other areas of medicine.
  • [MeSH-major] Monoclonal Gammopathy of Undetermined Significance
  • [MeSH-minor] Amyloidosis / epidemiology. Disease Progression. Hematologic Neoplasms / epidemiology. Humans. Incidence. Mass Screening. Osteoporosis / etiology. Paraproteins / analysis. Peripheral Nervous System Diseases / etiology. Prognosis. Risk. Risk Factors. Waldenstrom Macroglobulinemia / epidemiology

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  • (PMID = 21766546.001).
  • [ISSN] 0004-4849
  • [Journal-full-title] Boletín de la Asociación Médica de Puerto Rico
  • [ISO-abbreviation] Bol Asoc Med P R
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] Puerto Rico
  • [Chemical-registry-number] 0 / Paraproteins
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11. Fujimura T, Okuyama R, Ogawa E, Aiba S: Papuloerythroderma associated with monoclonal gammopathy of undetermined significance. J Dermatol; 2009 Apr;36(4):228-31
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Papuloerythroderma associated with monoclonal gammopathy of undetermined significance.
  • We describe a 73-year-old Japanese man with papuloerythroderma overlapped with monoclonal gammopathy of undetermined significance (MGUS).
  • A biochemical profile revealed the presence of immunoglobulin G kappa chain type monoclonal protein in the serum but the absence of hematological neoplasms.
  • We diagnosed the patient as papuloerythroderma with MGUS, and treated him with narrow-band ultraviolet B and topical steroid.
  • This case suggests an association between papuloerythroderma and MGUS.

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  • (PMID = 19348662.001).
  • [ISSN] 1346-8138
  • [Journal-full-title] The Journal of dermatology
  • [ISO-abbreviation] J. Dermatol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Immunoglobulin G; 0 / Immunoglobulin kappa-Chains; 1A63Z067C8 / diflucortolone valerate; K253365DXI / Diflucortolone
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12. Kyle RA, Rajkumar SV: Monoclonal gammopathy of undetermined significance. Clin Lymphoma Myeloma; 2005 Sep;6(2):102-14
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  • [Title] Monoclonal gammopathy of undetermined significance.
  • Monoclonal gammopathy of undetermined significance (MGUS) is characterized by the presence of a monoclonal protein (M-protein) without evidence of multiple myeloma (MM), Waldenstrom's macroglobulinemia (WM), amyloidosis (AL), or a related plasma cell proliferative disorder.
  • Monoclonal gammopathy of undetermined significance is found in approximately 3% of persons > 70 years of age and in about 1% of those > 50 years old.
  • In a series of 1384 patients from Southeastern Minnesota in whom MGUS was diagnosed at Mayo Clinic from 1960 through 1994, the risk of progression was 1% per year.
  • This risk of progression continued even after > or = 25 years of a stable M-protein.
  • The presence of a urine M-protein or the reduction of > or = 1 uninvolved immunoglobulins was not a risk factor for disease progression.
  • Patients must be monitored for progressive disease throughout their lives.
  • Variants of MGUS consist of IgM MGUS, biclonal gammopathies, triclonal gammopathies, idiopathic Bence Jones (light-chain) proteinuria, and IgD MGUS.
  • Monoclonal gammopathy of undetermined significance may be associated with many disorders, including lymphoproliferative diseases, leukemia, von Willebrand's disease, connective tissue diseases, and neurologic disorders.
  • [MeSH-minor] Aged. Amyloidosis / blood. Amyloidosis / classification. Amyloidosis / epidemiology. Disease Progression. Female. Humans. Immunoglobulin A / blood. Immunoglobulin Light Chains / blood. Immunoglobulin M / blood. Male. Middle Aged. Retrospective Studies. Risk Factors

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  • (PMID = 16231848.001).
  • [ISSN] 1557-9190
  • [Journal-full-title] Clinical lymphoma & myeloma
  • [ISO-abbreviation] Clin Lymphoma Myeloma
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA 107476; United States / NCI NIH HHS / CA / CA 62242
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Immunoglobulin A; 0 / Immunoglobulin Light Chains; 0 / Immunoglobulin M
  • [Number-of-references] 103
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13. Rajkumar SV, Lacy MQ, Kyle RA: Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. Blood Rev; 2007 Sep;21(5):255-65
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  • [Title] Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma.
  • Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic disorders characterized by monoclonal plasma cell proliferation in the bone marrow in the absence of end-organ damage.
  • [MeSH-minor] Disease Progression. Humans. Neovascularization, Pathologic. Prognosis. Risk Factors

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  • (PMID = 17367905.001).
  • [ISSN] 0268-960X
  • [Journal-full-title] Blood reviews
  • [ISO-abbreviation] Blood Rev.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA 107476; United States / NCI NIH HHS / CA / CA 62242
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Review
  • [Publication-country] Scotland
  • [Number-of-references] 70
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14. Kyle RA, Rajkumar SV: Monoclonal gammopathy of undetermined significance. Br J Haematol; 2006 Sep;134(6):573-89
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  • [Title] Monoclonal gammopathy of undetermined significance.
  • Significant advances have been made in our understanding of the natural history, pathogenesis, mechanisms of progression and prognosis of monoclonal gammopathy of undetermined significance (MGUS).
  • Although the overall incidence of MGUS progression is 1 per year, it is now possible to more accurately predict the risk of progression based on a new risk-stratification model.
  • Roughly 50% of MGUS may originate from primary translocation events at the heavy-chain immunoglobulin locus at chromosome 14q32.
  • In most of the remaining MGUS patients, the initiating event is associated with genomic instability that results in hyperdiploidy of certain odd numbered chromosomes.
  • Cytogenetically distinct subtypes of MGUS may carry significant differences in the risk of progression to malignancy.
  • New markers, such as measures of bone marrow angiogenesis and circulating plasma cells may be additional prognostic factors.
  • A better understanding of the mechanisms underlying the transition of normal plasma cells to the MGUS phenotype, and the transition of MGUS to myeloma or related malignancy, will help identify new risk factors for progression and new targets for chemopreventive interventions.
  • [MeSH-major] Monoclonal Gammopathy of Undetermined Significance
  • [MeSH-minor] Aged. Disease Progression. Female. Humans. Male. Prevalence. Prognosis

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  • (PMID = 16938117.001).
  • [ISSN] 0007-1048
  • [Journal-full-title] British journal of haematology
  • [ISO-abbreviation] Br. J. Haematol.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA 107476; United States / NCI NIH HHS / CA / CA 62242
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Review
  • [Publication-country] England
  • [Number-of-references] 104
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15. Dhodapkar MV, Bolejack V, Shaughnessy J, Matthews P, Pickering R, Qu P, Hoering A, Crowley J, Barlogie B, Southwest Oncology Group: Role of T-cell immunity to embryonal stem (ES) cell antigen SOX2 in the progression of myeloma. J Clin Oncol; 2009 May 20;27(15_suppl):8522

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  • [Title] Role of T-cell immunity to embryonal stem (ES) cell antigen SOX2 in the progression of myeloma.
  • : 8522 Background: Clinical outcome in patients (pts) with asymptomatic plasma-proliferative disorders, monoclonal gammopathy of undetermined significance (MGUS) and asymptomatic myeloma (AMM), is highly variable.
  • There is a need to identify specific tumor or host related features that predict the risk of disease progression.
  • In prior studies, we have shown that patients with MGUS commonly mount a T cell immune response against SOX2, an antigen critical for pluripotency of ES cells.
  • METHODS: Patients with MGUS/AMM were enrolled in a prospective observational clinical protocol (SWOG S0120).
  • The presence of T cell immunity to SOX2 in freshly isolated blood / marrow mononuclear cells was analyzed using an overlapping peptide library at study entry.
  • RESULTS: Anti-SOX2 T cell responses were detected in 39/109 (36%) pts tested.
  • Immunity to SOX2 correlated with features of lower risk including serum-M component < 1.5 g/dL (p=0.008), marrow plasmacytosis < 10% (p<0.001) and normal serum free light chain ratio (p=0.01).
  • CONCLUSIONS: These data demonstrate in the context of a prospective trial that T cell immunity to stem cell genes strongly correlates with a reduced risk of progression to clinical myeloma.
  • These data point to SOX2 as a potential target for the prevention of disease progression in MGUS/AMM.

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  • (PMID = 27960897.001).
  • [ISSN] 1527-7755
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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16. Kyle RA, Rajkumar SV: Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. Hematol Oncol Clin North Am; 2007 Dec;21(6):1093-113, ix
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  • [Title] Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma.
  • In 1978, the term "monoclonal gammopathy of undetermined significance" (MGUS) was introduced.
  • MGUS is defined as a serum monoclonal (M) protein less than 3.0 g/dL; less than 10% plasma cells in the bone marrow, if done; little or no M protein in the urine; and absence of lytic bone lesions, anemia, hypercalcemia or renal insufficiency.
  • This article discusses the recognition, prevalence, natural history, and progression of MGUS.
  • Management of the disease is discussed along with its association with other disorders.
  • [MeSH-major] Monoclonal Gammopathy of Undetermined Significance / diagnosis. Monoclonal Gammopathy of Undetermined Significance / physiopathology. Multiple Myeloma / physiopathology
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Disease Progression. Female. Follow-Up Studies. Humans. Incidence. Male. Middle Aged. Minnesota / epidemiology. Retrospective Studies

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  • (PMID = 17996590.001).
  • [ISSN] 0889-8588
  • [Journal-full-title] Hematology/oncology clinics of North America
  • [ISO-abbreviation] Hematol. Oncol. Clin. North Am.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA107476; United States / NCI NIH HHS / CA / CA62242
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] United States
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17. Decaux O, Laurat E, Perlat A, Cazalets C, Jego P, Grosbois B: Systemic manifestations of monoclonal gammopathy. Eur J Intern Med; 2009 Sep;20(5):457-61

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  • [Title] Systemic manifestations of monoclonal gammopathy.
  • Systemic manifestations of monoclonal gammopathies (MG) are rare but extremely varied.
  • The POEMS syndrome classically consists of polyneuropathy, organomegaly, endocrinopathy, monoclonal plasmocyte proliferation, and cutaneous manifestations.
  • These systemic manifestations can reveal classical MG-related disorders such as monoclonal gammopathy of undetermined significance (MGUS), solitary plasmocytoma, multiple myeloma, and Waldenstrom's disease.
  • They are due either to the chemicophysical properties of the monoclonal immunoglobulin, or to its antibody activity (especially against autoantigens), with potential therapeutic implications.
  • [MeSH-major] Paraproteinemias / complications. Paraproteinemias / diagnosis
  • [MeSH-minor] Hematologic Diseases / diagnosis. Hematologic Diseases / etiology. Hematologic Diseases / therapy. Humans. Nervous System Diseases / diagnosis. Nervous System Diseases / etiology. Nervous System Diseases / therapy. Skin Diseases / diagnosis. Skin Diseases / etiology. Skin Diseases / therapy

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  • [Copyright] 2008 European Federation of Internal Medicine.
  • (PMID = 19712843.001).
  • [ISSN] 1879-0828
  • [Journal-full-title] European journal of internal medicine
  • [ISO-abbreviation] Eur. J. Intern. Med.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] Netherlands
  • [Number-of-references] 49
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18. Bladé J, Rosiñol L, Cibeira MT, de Larrea CF: Pathogenesis and progression of monoclonal gammopathy of undetermined significance. Leukemia; 2008 Sep;22(9):1651-7
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  • [Title] Pathogenesis and progression of monoclonal gammopathy of undetermined significance.
  • In Caucasians, monoclonal gammopathy of undetermined significance (MGUS) is an age-related condition with prevalence as high as 3% in persons older than 50 years.
  • Compared with whites, blacks have around two- and threefold higher prevalence rates of MGUS and multiple myeloma (MM), respectively.
  • Risk of progression from MGUS to MM has been found to be very similar in whites and blacks.
  • On average, the transformation rate to a malignant monoclonal gammopathy is 1% per year, with the mechanisms of progression likely related to bone marrow microenvironment and/or the cytokine network.
  • The predictors of malignant transformation are the plasma cell mass (M-protein size and/or proportion of plasma cell in the bone marrow), IgA isotype, serum free light-chain ratio and 'evolving' type and ratio between phenotypically aberrant and normal bone marrow plasma cells.
  • [MeSH-major] Monoclonal Gammopathy of Undetermined Significance / etiology. Multiple Myeloma / etiology
  • [MeSH-minor] Cell Transformation, Neoplastic / pathology. Diagnosis, Differential. Disease Progression. Humans

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  • (PMID = 18668131.001).
  • [ISSN] 1476-5551
  • [Journal-full-title] Leukemia
  • [ISO-abbreviation] Leukemia
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] England
  • [Number-of-references] 63
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19. Gajos A, Kieliś W, Szadkowska I, Chmielowska E, Niewodniczy A, Bogucki A: [Acquired peripheral neuropathies associated with monoclonal gammopathy]. Neurol Neurochir Pol; 2007 Mar-Apr;41(2):169-75
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  • [Title] [Acquired peripheral neuropathies associated with monoclonal gammopathy].
  • [Transliterated title] Nabyte neuropatie obwodowe w przebiegu gammapatii monoklonalnych.
  • Monoclonal gammopathy is responsible for about 10% of acquired peripheral neuropathies of unknown origin.
  • Monoclonal gammopathy is the result of uncontrolled proliferation of a single clone of plasma cells producing the first class of immunoglobulin (M-protein).
  • Monoclonal gammopathies develop in malignancy, immunological disorders, chronic infections and as so-called "benign form" or monoclonal gammopathy of undetermined significance (MGUS).
  • Lymphoproliferative malignancy may develop in MGUS after many years of disease.
  • Patients with MGUS-associated neuropathy should be carefully evaluated, and if malignancy is not found the progress of the disease should be monitored.
  • We present four patients with peripheral neuropathy associated with monoclonal gammopathy.
  • These cases represent different forms of this type of neuropathy and well illustrate the necessity of looking for monoclonal gammopathies in peripheral neuropathy.
  • [MeSH-major] Immunoglobulin kappa-Chains / blood. Immunoglobulin lambda-Chains / blood. Paraproteinemias / complications. Paraproteinemias / diagnosis. Peripheral Nervous System Diseases / etiology

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  • (PMID = 17530580.001).
  • [ISSN] 0028-3843
  • [Journal-full-title] Neurologia i neurochirurgia polska
  • [ISO-abbreviation] Neurol. Neurochir. Pol.
  • [Language] pol
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] Poland
  • [Chemical-registry-number] 0 / Immunoglobulin A; 0 / Immunoglobulin G; 0 / Immunoglobulin M; 0 / Immunoglobulin kappa-Chains; 0 / Immunoglobulin lambda-Chains
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20. Scudla V, Budíková M, Pika T, Minarík J, Zemanová M, Bacovský J, Heincová V, Ceská myelomová skupina: [Comparison of serum levels of selected biological parameters in monoclonal gammopathy of undetermined significance and multiple myeloma]. Vnitr Lek; 2006 Mar;52(3):232-40
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  • [Title] [Comparison of serum levels of selected biological parameters in monoclonal gammopathy of undetermined significance and multiple myeloma].
  • [Transliterated title] Srovnání sérových hladin vybraných biologických ukazatelů u monoklonální gamapatie nejistého významu a mnohocetného myelomu.
  • PURPOSE OF STUDY: The study focuses on evaluation of differences in serum levels of selected biological indicators in monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM), primarily from the viewpoint of potential asset to clinical practice.
  • PATIENTS AND METHODOLOGY: The analyse set of 96 patients consisted of 30 individuals with MGUS and 66 patients with MM examined in the context of the disease diagnosis before therapy commencement.
  • Statistical examination was performed by Pearson and Fischer test, chi2-test, or nonparametric U-test pursuant to Mann-Whitney (p < 0.05).
  • RESULTS: Statistically significant differences were found between MGUS and MM in the case of serum level comparisons of sIL-6R (p = 0.02), ICTP (p = 0.001), sHGF (p = 0.001) and syndecan-1/sCD138 (p = 0.001), while no statistically significant differences were present in the case of sVCAM-1, sICAM-1, PINP, sOPG, sVEGF and sFas.
  • During the analysis of frequency of occurrence of abnormal values in the MM and MGUS groups, significant differences were found not only in the case of standard parameters, such as beta2-microglobulin, thymidinkinase, creatinin and albumin, but also in the case of sIL-6R, ICTP, sHGF and syndecan-1, but not in comparisons of the levels of sVCAM-1, sICAM-1, PINP, sOPG, sVEGF and sFas.
  • CONCLUSION: The analysis of behaviour of the 10 parameters, mostly intimately related to biological properties of clonal plasmatic cells or to changes of microclimate of bone marrow, effectively contributed to distinction between MGUS and MM only in the case of serum levels of sIL-6R, ICTP, sHGF and syndecan-l (sCD138), i.e. indicators with demonstrable relevance for MM prognosis assessment.

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  • (PMID = 16722154.001).
  • [ISSN] 0042-773X
  • [Journal-full-title] Vnitr̆ní lékar̆ství
  • [ISO-abbreviation] Vnitr Lek
  • [Language] cze
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] Czech Republic
  • [Chemical-registry-number] 0 / Biomarkers
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21. Scudla V, Budíková M, Petrová P, Minarík J, Pika T, Bacovský J, Adamová D, Langová K, Ceská myelomová skupina: [Analysis of serum levels of selected biological parameters in monoclonal gammopathy of undetermined significance and multiple myeloma]. Klin Onkol; 2010;23(3):171-81
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  • [Title] [Analysis of serum levels of selected biological parameters in monoclonal gammopathy of undetermined significance and multiple myeloma].
  • [Transliterated title] Analýza sérových hladin vybraných biologických ukazatelů u monoklonální gamapatie nejistého významu a mnohocetného myelomu.
  • BACKGROUNDS: The aim of the study was to evaluate the serum levels of 18 selected parameters in monoclonal gammopathy of undetermined significance, and the initial, asymptomatic phase of multiple myeloma, also from the point of view of the potential contribution to the differentiation of these two units.
  • MATERIALS AND METHODS: The analyzed 119-patient group consisted of 59 individuals with monoclonal gammopathy of undetermined significance and 60 patients with multiple myeloma assessed at the time of diagnosis before the start of the treatment.
  • Statistical evaluation was done using the Pearson chi-quadrat test and the U-test according to Mann-Whitney (p < 0.05).
  • RESULTS: Statistically significant differences between monoclonal gammopathy of undetermined significance and multiple myeloma were found in the case of serum levels of thymidine kinase (0.0002), ICTP (0.001), MIP-1 alpha (0.002), osteopontin (<0.0001), HGF (< 0.0001), syndecan-1 (<0.0001), and the kappa/lambda ratio (0.0002), while lower significance was found in the case of angiogenin (0.031) and endostatin (0.011).
  • Statistically non-significant differences between multiple myeloma and monoclonal gammopathy of undetermined significance were within the serum levels of IGF-1, osteocalcin, bALP, PINP, OPG, MIP-1 beta, IL-17, parathormon and VEGF.
  • CONCLUSION: Statistical analysis revealed significant differences between monoclonal gammopathy of undetermined significance and multiple myeloma in 9 of the 18 evaluated parameters.
  • A certain contribution in the discrimination of multiple myeloma from monoclonal gammopathy of undetermined significance was found in markedly increased serum levels of thymidine kinase, MIP-1 alpha, osteopontin, HGF and significant pathology of the kappa/lambda index.
  • [MeSH-major] Biomarkers / blood. Multiple Myeloma / diagnosis. Paraproteinemias / diagnosis

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  • (PMID = 20608327.001).
  • [ISSN] 0862-495X
  • [Journal-full-title] Klinická onkologie : casopis Ceské a Slovenské onkologické spolecnosti
  • [ISO-abbreviation] Klin Onkol
  • [Language] cze
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] Czech Republic
  • [Chemical-registry-number] 0 / Biomarkers; 0 / Biomarkers, Tumor
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22. Cohen AL, Sarid R: The relationship between monoclonal gammopathy of undetermined significance and venous thromboembolic disease. Thromb Res; 2010 Mar;125(3):216-9
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  • [Title] The relationship between monoclonal gammopathy of undetermined significance and venous thromboembolic disease.
  • INTRODUCTION: Monoclonal gammopathy of undetermined significance (MGUS) has been proposed to be a risk factor for venous thromboembolic disease (VTE).
  • However, no series published to date has been population-based or included a control group with similar comorbidities to people with MGUS.
  • PATIENTS/METHODS: We reviewed the records of all the male veterans in a single VA healthcare system with MGUS between January 1, 1996 and December 31, 2005.
  • We compared the rate of VTE in 166 patients with MGUS with the rate of VTE in an age-matched control group of 465 patients who had tested negative for monoclonal gammopathy by serum protein electrophoresis (SPEP).
  • RESULTS: The VTE rate in the MGUS group was 2.2 per 100 person-years, which was not significantly different from the rate in the control group, 1.4 per 100 person-years (HR 1.38, CI 0.63-3.01, p=0.42).
  • Most VTE events occurred within 4 months of the diagnosis of MGUS.
  • In univariate analysis, albumin level (HR 0.21, CI 0.1-0.41, p<0.001), abnormal leukocyte count (HR 2.53, CI 1.09-5.86, p=0.03), and history of prior VTE (HR 4.41, CI 1.69-11.54, p=0.003) were associated with increased risk of VTE.
  • On multivariate analysis, albumin level and history of prior VTE remained significant, but presence of MGUS was still not significantly associated with VTE risk.
  • CONCLUSION: Our results suggest that the increased rate of VTE in people with MGUS may be primarily due to other underlying conditions that led to testing for a monoclonal gammopathy rather than to the monoclonal gammopathy itself.
  • [MeSH-major] Monoclonal Gammopathy of Undetermined Significance / complications. Venous Thrombosis / complications

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  • [Copyright] (c) 2009 Elsevier Ltd. All rights reserved.
  • (PMID = 19193398.001).
  • [ISSN] 1879-2472
  • [Journal-full-title] Thrombosis research
  • [ISO-abbreviation] Thromb. Res.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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23. Gregersen H, Jensen P, Gislum M, Jørgensen B, Sørensen HT, Nørgaard M: Fracture risk in patients with monoclonal gammopathy of undetermined significance. Br J Haematol; 2006 Oct;135(1):62-7
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  • [Title] Fracture risk in patients with monoclonal gammopathy of undetermined significance.
  • Little information is available on the risk of fractures in patients with monoclonal gammopathy of undetermined significance (MGUS).
  • We identified 1535 patients with MGUS between 1978 and 2003 in North Jutland County, Denmark.
  • In the MGUS cohort, 187 first-time fractures were identified during 9754 person-years of follow-up, corresponding to an incidence rate of 19/1000 person-years.
  • The adjusted relative risk for fractures among MGUS patients compared with population controls was 1.4 [95% confidence interval (CI), 1.2-1.6].
  • Six of the 187 MGUS patients with fractures were later diagnosed with malignant transformation.
  • Relative risks for fractures were increased in IgG-type MGUS [1.3 (95% CI,1.1-1.6)], IgM-type MGUS [1.6 (95% CI, 1.1-2.2)] and MGUS with kappa light chain [1.4 (95% CI, 1.1-1.7)].
  • MGUS patients had an increased risk of fractures, which could not be explained by comorbidity, advanced age, gender or malignant transformation.

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  • (PMID = 16925792.001).
  • [ISSN] 0007-1048
  • [Journal-full-title] British journal of haematology
  • [ISO-abbreviation] Br. J. Haematol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
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24. Kyle RA, Rajkumar SV: Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. Curr Hematol Malig Rep; 2010 Apr;5(2):62-9
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma.
  • Monoclonal gammopathy of undetermined significance (MGUS) is characterized by the presence of a serum monoclonal (M) protein level less than 3 g/dL, less than 10% clonal plasma cells in the bone marrow, and the absence of hypercalcemia, renal insufficiency, anemia, or bone lesions attributable to a clonal plasma cell disorder.
  • Patients may be tested for a monoclonal gammopathy by serum protein electrophoresis, immunofixation, and the free light chain (FLC) assay.
  • The prevalence of MGUS is 3% for persons more than 50 years of age and 5% in those more than 70 years of age.
  • The risk of progression to multiple myeloma or a related disorder is 1% per year.
  • The size and type of M protein, the number of bone marrow plasma cells, and the results of the FLC ratio are independent risk factors for progression.
  • Smoldering multiple myeloma (SMM) is a more advanced premalignant phase than MGUS and is characterized by more than 3 g/dL of serum M protein, more than 10% clonal plasma cells in the bone marrow, or both, with no evidence of end-organ damage.

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  • (PMID = 20425398.001).
  • [ISSN] 1558-822X
  • [Journal-full-title] Current hematologic malignancy reports
  • [ISO-abbreviation] Curr Hematol Malig Rep
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / P01 CA062242; United States / NCI NIH HHS / CA / R01 CA107476; United States / NCI NIH HHS / CA / CA 62242; United States / NCI NIH HHS / CA / CA107476
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Review
  • [Publication-country] United States
  • [Number-of-references] 41
  • [Other-IDs] NLM/ NIHMS546318; NLM/ PMC3904304
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25. Kyle RA, Therneau TM, Rajkumar SV, Larson DR, Plevak MF, Offord JR, Dispenzieri A, Katzmann JA, Melton LJ 3rd: Prevalence of monoclonal gammopathy of undetermined significance. N Engl J Med; 2006 Mar 30;354(13):1362-9
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Prevalence of monoclonal gammopathy of undetermined significance.
  • BACKGROUND: The prevalence of monoclonal gammopathy of undetermined significance (MGUS), a premalignant plasma-cell disorder, among persons 50 years of age or older has not been accurately determined.
  • We used sensitive laboratory techniques to ascertain the prevalence of MGUS in a large population in a well-defined geographic area.
  • Agarose-gel electrophoresis was performed on all serum samples, and any serum sample with a discrete band of monoclonal protein or thought to have a localized band was subjected to immunofixation.
  • MGUS was identified in 694 (3.2 percent) of these persons.
  • Age-adjusted rates were higher in men than in women (4.0 percent vs. 2.7 percent, P<0.001).
  • The prevalence of MGUS was 5.3 percent among persons 70 years of age or older and 7.5 percent among those 85 years of age or older.
  • The concentration of monoclonal immunoglobulin was less than 1.0 g per deciliter in 63.5 percent and at least 2.0 g per deciliter in only 4.5 percent of 694 persons.
  • The concentration of uninvolved immunoglobulins was reduced in 27.7 percent of 447 persons tested, and 21.5 percent of 79 tested had a monoclonal urinary light chain.
  • CONCLUSIONS: Among residents of Olmsted County, Minnesota, MGUS was found in 3.2 percent of persons 50 years of age or older and 5.3 percent of persons 70 years of age or older.

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  • [Copyright] Copyright 2006 Massachusetts Medical Society.
  • [CommentIn] N Engl J Med. 2006 Jun 29;354(26):2832; author reply 2832 [16807426.001]
  • (PMID = 16571879.001).
  • [ISSN] 1533-4406
  • [Journal-full-title] The New England journal of medicine
  • [ISO-abbreviation] N. Engl. J. Med.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA 107476; United States / NCI NIH HHS / CA / CA 62242
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Immunoglobulin A; 0 / Immunoglobulin G; 0 / Immunoglobulin M
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26. Landgren O, Katzmann JA, Hsing AW, Pfeiffer RM, Kyle RA, Yeboah ED, Biritwum RB, Tettey Y, Adjei AA, Larson DR, Dispenzieri A, Melton LJ 3rd, Goldin LR, McMaster ML, Caporaso NE, Rajkumar SV: Prevalence of monoclonal gammopathy of undetermined significance among men in Ghana. Mayo Clin Proc; 2007 Dec;82(12):1468-73
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Prevalence of monoclonal gammopathy of undetermined significance among men in Ghana.
  • OBJECTIVE: To determine the prevalence of monoclonal gammopathy of undetermined significance (MGUS), a precursor of multiple myeloma (MM), in Ghanaian men vs white men and to test for evidence to support an underlying race-related predisposition of the 2-fold higher prevalence of MGUS in African Americans vs whites.
  • Age-adjusted and standardized (to the 2000 world population) prevalence estimates of MGUS and 95% confidence intervals (CIs) were computed in the Ghanaian men and compared with MGUS prevalence in 7996 white men from Minnesota.
  • Associations between selected characteristics and MGUS prevalence were assessed by the Fisher exact test and logistic regression models.
  • RESULTS: Of the 917 study participants, 54 were found to have MGUS, yielding an age-adjusted prevalence of 5.84 (95% CI, 4.27-7.40) per 100 persons.
  • The concentration of monoclonal immunoglobulin was undetectable in 41 (76%) of the 54 MGUS cases, less than 1 g/dL in 10 patients (19%), and 1 g/dL or more in only 3 patients (6%).
  • Compared with white men, the age-adjusted prevalence of MGUS was 1.97-fold (95% CI, 1.94-2.00) higher in Ghanaian men.
  • CONCLUSION: The prevalence of MGUS in Ghanaian men was twice that in white men, supporting the hypothesis that race-related genetic susceptibility could explain the higher rates of MGUS in black populations.
  • An improved understanding of MGUS and MM pathophysiology would facilitate the development of strategies to prevent progression of MGUS to MM.
  • [MeSH-minor] Age Distribution. Aged. European Continental Ancestry Group / statistics & numerical data. Genetic Predisposition to Disease. Ghana / epidemiology. Humans. Male. Middle Aged. Minnesota / epidemiology. Prevalence. Socioeconomic Factors

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  • [CommentIn] Mayo Clin Proc. 2008 May;83(5):601-2; author reply 602-3 [18452695.001]
  • [CommentIn] Mayo Clin Proc. 2007 Dec;82(12):1457-9 [18053450.001]
  • (PMID = 18053453.001).
  • [ISSN] 0025-6196
  • [Journal-full-title] Mayo Clinic proceedings
  • [ISO-abbreviation] Mayo Clin. Proc.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA107-476-03; United States / NCI NIH HHS / CA / CA62242; United States / Intramural NIH HHS / /
  • [Publication-type] Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
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27. Korać P, Peran I, Skrtić A, Ajduković R, Kristo DR, Dominis M: FOXP1 expression in monoclonal gammopathy of undetermined significance and multiple myeloma. Pathol Int; 2009 May;59(5):354-8
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] FOXP1 expression in monoclonal gammopathy of undetermined significance and multiple myeloma.
  • Multiple myeloma (MM) is a clonal disorder of terminally differentiated B cells.
  • In some cases the premalignant state is monoclonal gammopathy of undetermined significance (MGUS).
  • Neoplastic plasma cells in both entities carry multiple and complex chromosomal abnormalities that make understanding of the disease development difficult.
  • New insight into malignant mechanisms that underlie multiple myeloma may come from forkhead box P1 transcription factor (FOXP1) analysis in neoplastic plasma cells.
  • FOXP1 is known to be important for B-cell maturation and differentiation and could play a significant role in plasma cell tumors.
  • The purpose of the present study was therefore to analyze FOXP1 protein presence and FOXP1 gene abnormalities in 13 cases of MGUS and 60 cases of MM.
  • It was found that FOXP1 protein was expressed in neoplastic plasma cells, unlike in their normal counterparts, and that additional FOXP1 gene copies could be found in both MGUS and MM.
  • Based on FOXP1 presence in MM and its role in diffuse large B-cell lymphoma and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, FOXP1 might play an important role in plasma cell neoplasm.
  • [MeSH-major] Forkhead Transcription Factors / metabolism. Monoclonal Gammopathy of Undetermined Significance / metabolism. Multiple Myeloma / metabolism. Repressor Proteins / metabolism

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  • (PMID = 19432679.001).
  • [ISSN] 1440-1827
  • [Journal-full-title] Pathology international
  • [ISO-abbreviation] Pathol. Int.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Australia
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / FOXP1 protein, human; 0 / Forkhead Transcription Factors; 0 / Repressor Proteins
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28. Muslimani AA, Spiro TP, Chaudhry AA, Taylor HC, Jaiyesimi I, Daw HA: Venous thromboembolism in patients with monoclonal gammopathy of undetermined significance. Clin Adv Hematol Oncol; 2009 Dec;7(12):827-32

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Venous thromboembolism in patients with monoclonal gammopathy of undetermined significance.
  • Monoclonal gammopathy of undetermined significance (MGUS) is defined by the presence of a serum M-protein at a concentration of 3 g/dL or less, with less than 10% plasma cells in the bone marrow, and the absence of lytic bone lesions, anemia, hypercalcemia, and renal insufficiency related to the plasma cell proliferative process.
  • The annual risk of MGUS progressing to a symptomatic plasma cell proliferation or other related malignancy is approximately 1%.
  • In this retrospective study of MGUS patients, VTE was seen in 8% (9/112) of patients, a rate that is 22.8-fold higher than that in the general population (P is less than .001).
  • Although many studies have identified VTE as a marker for subsequent malignancy, we did not find a significant difference in the incidence of VTE as a function of the risk factor group.
  • [MeSH-major] Monoclonal Gammopathy of Undetermined Significance / complications. Venous Thromboembolism / epidemiology
  • [MeSH-minor] Disease Progression. Humans. Retrospective Studies. Risk Assessment. Survival Rate

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  • (PMID = 20332755.001).
  • [ISSN] 1543-0790
  • [Journal-full-title] Clinical advances in hematology & oncology : H&O
  • [ISO-abbreviation] Clin Adv Hematol Oncol
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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29. Bladé J, Rosiñol L: Smoldering multiple myeloma and monoclonal gammopathy of undetermined significance. Curr Treat Options Oncol; 2006 May;7(3):237-45
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Smoldering multiple myeloma and monoclonal gammopathy of undetermined significance.
  • Smoldering multiple myeloma (SMM) consists of the presence of a serum M protein of 30 g/L or more and/or 10% or more bone marrow plasma cells (BMPCs), with no clinical manifestations or symptoms of myeloma.
  • The main factors for progression are the plasma cell mass (M-protein size and percent of BMPCs), the spinal MRI pattern, the plasma cell proliferative index, and the variant of SMM ("evolving" vs "nonevolving").
  • Although treatment with thalidomide is promising (based on the results of two phase II trials), outside the context of a clinical trial, a watch-and-wait approach with clinical evaluation every 4 months is recommended until evident symptomatic disease progression occurs.
  • Patients with monoclonal gammopathy of undetermined significance (MGUS) have a serum M protein lower than 30 g/L and a proportion of BMPCs of less than 10%, with no clinical findings or symptoms attributable to the monoclonal gammopathy.
  • MGUS has a high prevalence, and its annual rate of malignant transformation is 1%, such that the actuarial probability of progression to a symptomatic monoclonal gammopathy at 25 years of follow-up is as high as 40%.
  • The factors associated with a higher probability of malignant transformation are a relatively high plasma cell mass, immunoglobulin A M-protein type, and the "evolving" variant.
  • It is recommended that patients with MGUS are monitored annually.
  • Importantly, patients with asymptomatic monoclonal gammopathies must not be treated before the development of overt multiple myeloma.
  • [MeSH-major] Monoclonal Gammopathy of Undetermined Significance / pathology. Multiple Myeloma / pathology

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  • (PMID = 16615879.001).
  • [ISSN] 1527-2729
  • [Journal-full-title] Current treatment options in oncology
  • [ISO-abbreviation] Curr Treat Options Oncol
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] United States
  • [Number-of-references] 46
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30. Tzelikis PF, Laibson PR, Ribeiro MP, Rapuano CJ, Hammersmith KM, Cohen EJ: Ocular copper deposition associated with monoclonal gammopathy of undetermined significance: case report. Arq Bras Oftalmol; 2005 Jul-Aug;68(4):539-41
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Ocular copper deposition associated with monoclonal gammopathy of undetermined significance: case report.
  • To report a case of ocular copper deposition in both eyes at the level of Descemet's membrane associated with a monoclonal gammopathy of undetermined significance (MGUS).
  • Flow cytometric analysis of the marrow aspirate identified a monoclonal plasma cell population that represents approximately 2% of the total marrow cells consistent with the diagnosis of monoclonal gammopathy of undetermined significance.
  • Copper deposits at the level of Descemet's membrane may be a finding in a patient with monoclonal gammopathy of undetermined significance.
  • [MeSH-major] Copper / analysis. Descemet Membrane / chemistry. Monoclonal Gammopathy of Undetermined Significance / diagnosis. Paraproteinemias / diagnosis

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  • (PMID = 16322842.001).
  • [ISSN] 0004-2749
  • [Journal-full-title] Arquivos brasileiros de oftalmologia
  • [ISO-abbreviation] Arq Bras Oftalmol
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Brazil
  • [Chemical-registry-number] 789U1901C5 / Copper
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31. Sethi S, Zand L, Leung N, Smith RJ, Jevremonic D, Herrmann SS, Fervenza FC: Membranoproliferative glomerulonephritis secondary to monoclonal gammopathy. Clin J Am Soc Nephrol; 2010 May;5(5):770-82
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Membranoproliferative glomerulonephritis secondary to monoclonal gammopathy.
  • Autoimmune diseases and chronic infections, such as hepatitis C, are commonly recognized causes of MPGN; however, monoclonal gammopathy is a less widely recognized cause of MPGN.
  • DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We reviewed all renal biopsies of MPGN in Mayo Clinic patients during a 6-year period to determine the association of monoclonal gammopathy with MPGN.
  • Results were correlated with electrophoresis studies and bone marrow biopsies to clarify the relationship between MPGN and gammopathies.
  • Of the 81 hepatitis-negative patients, 13 were not evaluated for gammopathies.
  • Of the remaining 68 patients, 28 (41.1%) had serum and/or urine electrophoresis studies positive for monoclonal gammopathy.
  • Serum immunofixation electrophoresis was the most sensitive method for diagnosing monoclonal gammopathy.
  • Renal biopsy showed a membranoproliferative pattern of injury; immunofluorescence microscopy was often instrumental in diagnosing the underlying gammopathy.
  • On the basis of the bone marrow biopsy, monoclonal gammopathy of undetermined significance was the most common entity associated with MPGN.
  • Other, less common causes included multiple myeloma, low-grade B cell lymphoma, and chronic lymphocytic leukemia.
  • CONCLUSIONS: Monoclonal gammopathy is an important and common cause of MPGN; therefore, all patients with a diagnosis of MPGN should be evaluated for an underlying monoclonal gammopathy.

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  • (PMID = 20185597.001).
  • [ISSN] 1555-905X
  • [Journal-full-title] Clinical journal of the American Society of Nephrology : CJASN
  • [ISO-abbreviation] Clin J Am Soc Nephrol
  • [Language] ENG
  • [Grant] United States / NIDDK NIH HHS / DK / R01 DK074409; United States / NIDDK NIH HHS / DK / DK074409
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal
  • [Other-IDs] NLM/ PMC2863981
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32. Landgren O: Monoclonal gammopathy of undetermined significance and smoldering myeloma: new insights into pathophysiology and epidemiology. Hematology Am Soc Hematol Educ Program; 2010;2010:295-302
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Monoclonal gammopathy of undetermined significance and smoldering myeloma: new insights into pathophysiology and epidemiology.
  • Routine screening for monoclonal gammopathy of undetermined significance (MGUS) is not indicated.
  • Despite this fact, MGUS is a common finding in medical practice.
  • Almost all individuals diagnosed with MGUS represent incidental cases diagnosed when physicians order serum protein electrophoresis, immunofixation, or both, as part of the work-up of a number of common symptoms and laboratory abnormalities.
  • In the past years, several novel insights have been gained in the area of multiple myeloma (MM) precursor disease.

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  • (PMID = 21239809.001).
  • [ISSN] 1520-4383
  • [Journal-full-title] Hematology. American Society of Hematology. Education Program
  • [ISO-abbreviation] Hematology Am Soc Hematol Educ Program
  • [Language] ENG
  • [Grant] United States / Intramural NIH HHS / /
  • [Publication-type] Journal Article; Research Support, N.I.H., Intramural; Review
  • [Publication-country] United States
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33. Landgren O, Gridley G, Turesson I, Caporaso NE, Goldin LR, Baris D, Fears TR, Hoover RN, Linet MS: Risk of monoclonal gammopathy of undetermined significance (MGUS) and subsequent multiple myeloma among African American and white veterans in the United States. Blood; 2006 Feb 1;107(3):904-6
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Risk of monoclonal gammopathy of undetermined significance (MGUS) and subsequent multiple myeloma among African American and white veterans in the United States.
  • A few small studies have reported a higher prevalence of monoclonal gammopathy of undetermined significance (MGUS) in African Americans versus whites.
  • Etiologic factors for MGUS and determinants for transformation of MGUS to MM are unknown.
  • We quantified the prevalence of MGUS and subsequent risk of MM among 4 million African American and white male veterans admitted to Veterans Affairs (VA) hospitals.
  • The age-adjusted prevalence ratio of MGUS in African Americans compared with whites was 3.0 (2.7-3.3 95% confidence interval).
  • Among 2046 MGUS cases, the estimated cumulative risk of MM during the first 10 years of follow-up was similar (P = .37) for African Americans (17%) and whites (15%).
  • In the largest study to date, we suggest that the excess risk of MM in African Americans results from an increase in risk of MGUS rather than an increased risk of progression from MGUS to MM.

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  • [Cites] N Engl J Med. 2002 Feb 21;346(8):564-9 [11856795.001]
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  • (PMID = 16210333.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] ENG
  • [Grant] United States / Intramural NIH HHS / /
  • [Publication-type] Comparative Study; Journal Article; Research Support, N.I.H., Intramural
  • [Publication-country] United States
  • [Other-IDs] NLM/ PMC1895893
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34. Olteanu H, Wang HY, Chen W, McKenna RW, Karandikar NJ: Immunophenotypic studies of monoclonal gammopathy of undetermined significance. BMC Clin Pathol; 2008;8:13
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  • [Title] Immunophenotypic studies of monoclonal gammopathy of undetermined significance.
  • BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) is a common plasma cell dyscrasia, comprising the most indolent form of monoclonal gammopathy.
  • However, approximately 25% of MGUS cases ultimately progress to plasma cell myeloma (PCM) or related diseases.
  • In this study, we examined the immunophenotypic differences of plasma cells in MGUS and PCM.
  • METHODS: Bone marrow specimens from 32 MGUS patients and 32 PCM patients were analyzed by 4-color flow cytometry, using cluster analysis of ungated data, for the expression of several markers, including CD10, CD19, CD20, CD38, CD45, CD56 and surface and intracellular immunoglobulin light chains.
  • RESULTS: All MGUS patients had two subpopulations of plasma cells, one with a "normal" phenotype [CD19(+), CD56(-), CD38(bright +)] and one with an aberrant phenotype [either CD19(-)/CD56(+) or CD19(-)/CD56(-)].
  • The normal subpopulation ranged from 4.4 to 86% (mean 27%) of total plasma cells.
  • Only 20 of 32 PCM cases showed an identifiable normal subpopulation at significantly lower frequency [range 0-32%, mean 3.3%, p << 0.001].
  • The plasma cells in PCM were significantly less likely to express CD19 [1/32 (3.1%) vs. 13/29 (45%), p << 0.001] and more likely to express surface immunoglobulin [21/32 (66%) vs. 3/28 (11%), p << 0.001], compared to MGUS.
  • Those expressing CD19 did so at a significantly lower level than in MGUS, with no overlap in mean fluorescence intensities [174 +/- 25 vs. 430 +/- 34, p << 0.001].
  • Two of the six MGUS cases (33%) with >90% CD19(-) plasma cells showed progression of disease, whereas none of the cases with >10% CD19(+) plasma cells evolved to PCM.
  • CONCLUSION: MGUS cases with potential for disease progression appeared to lack CD19 expression on >90% of their plasma cells, displaying an immunophenotypic profile similar to PCM plasma cells.
  • A higher relative proportion of CD19(+) plasma cells in MGUS may be associated with a lower potential for disease progression.

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  • (PMID = 19040735.001).
  • [ISSN] 1472-6890
  • [Journal-full-title] BMC clinical pathology
  • [ISO-abbreviation] BMC Clin Pathol
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Other-IDs] NLM/ PMC2606678
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35. de Alba Campomanes AG, Rutar T, Crawford JB, Seiff S, Goodman D, Grenert J: Crystal-storing histiocytosis and crystalline keratopathy caused by monoclonal gammopathy of undetermined significance. Cornea; 2009 Oct;28(9):1081-4
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  • [Title] Crystal-storing histiocytosis and crystalline keratopathy caused by monoclonal gammopathy of undetermined significance.
  • PURPOSE: The purpose of this study was to report the occurrence of crystalline keratopathy and of orbital infiltrative disease resulting from crystal-storing histiocytosis (CSH) in a patient with monoclonal gammopathy of undetermined significance.
  • METHODS: The authors conducted a review of a medical record and immunohistopathologic studies.
  • The systemic evaluation was consistent with monoclonal gammopathy of undetermined significance.
  • For unknown reasons, in this patient, a systemic immunologic disorder led to lambda light chain abnormalities with histiocyte infiltration of the orbit and corneal deposition.
  • Although CSH is rare, it should be part of the differential diagnosis of orbital infiltrative disease with or without crystalline keratopathy.
  • [MeSH-major] Corneal Diseases / etiology. Histiocytosis / etiology. Monoclonal Gammopathy of Undetermined Significance / complications

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  • (PMID = 19724196.001).
  • [ISSN] 1536-4798
  • [Journal-full-title] Cornea
  • [ISO-abbreviation] Cornea
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Immunoglobulin lambda-Chains
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36. Kovarova L, Buresova I, Buchler T, Suska R, Pour L, Zahradova L, Penka M, Hajek R: Phenotype of plasma cells in multiple myeloma and monoclonal gammopathy of undetermined significance. Neoplasma; 2009;56(6):526-32
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Phenotype of plasma cells in multiple myeloma and monoclonal gammopathy of undetermined significance.
  • Flow cytometry is a useful tool for the analysis of plasma cells in monoclonal gammopathies.
  • The aim of this study was to find possibilities and limits of multicolour flow cytometry in diagnostics of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) and to identify parameters that could be used to differentiate between these two disorders.
  • Surface markers CD38 and CD138 were used for identification of plasma cells, CD19 and CD56 further distinguished normal and abnormal plasma cells, respectively.
  • The percentage of circulating plasma cells in peripheral blood was lower in MGUS patients then in MM (p<0,001) In bone marrow, the percentage of residual polyclonal CD19 plasma cell was higher (p<0,001) and the percentage of malignant monoclonal CD56 plasma cell was lower (p<0,001) in MGUS than in MM.
  • In conclusion, flow cytometry is relatively quick and effective method for analysis of plasma cells thus immunophenotyping can significantly contribute to the differential diagnosis of plasma cell proliferations.
  • [MeSH-major] Multiple Myeloma / diagnosis. Paraproteinemias / diagnosis. Plasma Cells / pathology

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  • (PMID = 19728762.001).
  • [ISSN] 0028-2685
  • [Journal-full-title] Neoplasma
  • [ISO-abbreviation] Neoplasma
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Slovakia
  • [Chemical-registry-number] 0 / Antigens, CD19; 0 / Antigens, CD56; 0 / Syndecan-1; EC 3.2.2.5 / Antigens, CD38
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37. Wolkersdörfer GW, Haase M, Morgner A, Baretton G, Miehlke S: Monoclonal gammopathy of undetermined significance and Russell body formation in Helicobacter pylori gastritis. Helicobacter; 2006 Oct;11(5):506-10
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  • [Title] Monoclonal gammopathy of undetermined significance and Russell body formation in Helicobacter pylori gastritis.
  • BACKGROUND: Infection by Helicobacter pylori has been linked to monoclonal gammopathy of undetermined significance (MGUS).
  • MGUS is thought to develop due to chronic antigenic stimulation in people with a specific genetic predisposition.
  • Histopathologic findings revealed infiltration with plasma cells containing accumulated condensed intercisternal immunoglobulins, the so-called 'Russell bodies'.
  • In addition, MGUS was present with total immunoglobulins within the normal range but a significantly decreased serum concentration of IgG subtype 3.
  • Molecular analyses demonstrated IgH formation, T-cell receptor gamma rearrangement, and alterations within the IgHG3 gene sequence.
  • Following H. pylori eradication, gastritis and dyspepsia gradually resolved but MGUS persisted for at least 22 months.
  • CONCLUSIONS: This is the first report to demonstrate that upon infection with H. pylori, an impaired secretory capacity of plasma cells due to specific molecular changes can present as Russell body gastritis.
  • The molecular findings question a pathogenetic link between Russell bodies and H. pylori, but suggest genetic alterations in the immunoglobulin locus as the possible cause for both MGUS and Russell body gastritis.

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  • (PMID = 16961813.001).
  • [ISSN] 1083-4389
  • [Journal-full-title] Helicobacter
  • [ISO-abbreviation] Helicobacter
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
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38. Jo DH, Oh JY, Kim MK, Heo JW, Lee JH, Wee WR: Aspergillus fumigatus scleritis associated with monoclonal gammopathy of undetermined significance. Korean J Ophthalmol; 2010 Jun;24(3):175-8
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  • [Title] Aspergillus fumigatus scleritis associated with monoclonal gammopathy of undetermined significance.
  • On systemic work-up including serum and urine electrophoresis studies, the serum monoclonal protein of immunoglobulin G was detected.
  • The patient was diagnosed with monoclonal gammopathy of undetermined significance and fungal scleritis.
  • [MeSH-minor] Aged. Amphotericin B / administration & dosage. Antifungal Agents / administration & dosage. Disease Progression. Eye Enucleation. Female. Humans. Injections, Intraocular. Sclera / diagnostic imaging. Sclera / pathology. Ultrasonography. Vitrectomy

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  • (PMID = 20532146.001).
  • [ISSN] 2092-9382
  • [Journal-full-title] Korean journal of ophthalmology : KJO
  • [ISO-abbreviation] Korean J Ophthalmol
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Korea (South)
  • [Chemical-registry-number] 0 / Antifungal Agents; 7XU7A7DROE / Amphotericin B
  • [Other-IDs] NLM/ PMC2882083
  • [Keywords] NOTNLM ; Aspergillus fumigatus / Monoclonal gammopathy of undetermined significance / Scleritis
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39. Lalive PH, Passweg JR, Kuntzer T: [Neuropathy associated with monoclonal gammopathy (dysglobulinemia)]. Rev Med Suisse; 2009 Apr 29;5(201):962-4, 966-7
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  • [Title] [Neuropathy associated with monoclonal gammopathy (dysglobulinemia)].
  • [Transliterated title] Neuropathies associées aux gammapathies monoclonales (dysglobulinémies).
  • Neurological complications of monoclonal gammopathy, or dysglobulinemia, are typically affecting the peripheral nerve.
  • The clinical course is often chronic and progressive and requires a precise diagnosis of the type of plasma cell disorder associated with the neuropathy, to investigate other organs manifestations and to assess the presence of specific markers.

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  • (PMID = 19476059.001).
  • [ISSN] 1660-9379
  • [Journal-full-title] Revue médicale suisse
  • [ISO-abbreviation] Rev Med Suisse
  • [Language] fre
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] Switzerland
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40. Landgren O, Kyle RA, Hoppin JA, Beane Freeman LE, Cerhan JR, Katzmann JA, Rajkumar SV, Alavanja MC: Pesticide exposure and risk of monoclonal gammopathy of undetermined significance in the Agricultural Health Study. Blood; 2009 Jun 18;113(25):6386-91
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  • [Title] Pesticide exposure and risk of monoclonal gammopathy of undetermined significance in the Agricultural Health Study.
  • We included 678 men (30-94 years) from a well-characterized prospective cohort of restricted-use pesticide applicators to assess the risk of monoclonal gammopathy of undetermined significance (MGUS).
  • Age-adjusted prevalence estimates of MGUS were compared with MGUS prevalence in 9469 men from Minnesota.
  • Associations between pesticide exposures and MGUS prevalence were assessed by logistic regression models adjusted for age and education level.
  • Among study participants older than 50 years (n = 555), 38 were found to have MGUS, yielding a prevalence of 6.8% (95% CI, 5.0%-9.3%).
  • Compared with men from Minnesota, the age-adjusted prevalence of MGUS was 1.9-fold (95% CI, 1.3- to 2.7-fold) higher among male pesticide applicators.
  • Among applicators, a 5.6-fold (95% CI, 1.9- to 16.6-fold), 3.9-fold (95% CI, 1.5- to 10.0-fold), and 2.4-fold (95% CI, 1.1- to 5.3-fold) increased risk of MGUS prevalence was observed among users of the chlorinated insecticide dieldrin, the fumigant mixture carbon-tetrachloride/carbon disulfide, and the fungicide chlorothalonil, respectively.
  • In summary, the prevalence of MGUS among pesticide applicators was twice that in a population-based sample of men from Minnesota, adding support to the hypothesis that specific pesticides are causatively linked to myelomagenesis.

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  • (PMID = 19387005.001).
  • [ISSN] 1528-0020
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] ENG
  • [Grant] United States / NIEHS NIH HHS / ES / Z01-ES049030; United States / NCI NIH HHS / CP / Z01-CP010119; United States / Intramural NIH HHS / / ; United States / NIEHS NIH HHS / ES / Z01 ES049030; United States / NCI NIH HHS / CA / P01 CA062242; United States / NCI NIH HHS / CA / CA 107476; United States / NCI NIH HHS / CP / Z01 CP010119; United States / NCI NIH HHS / CA / R01 CA107476; United States / NCI NIH HHS / CA / CA 62242
  • [Publication-type] Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Nitriles; 0 / Pesticides; CL2T97X0V0 / Carbon Tetrachloride; I0246D2ZS0 / Dieldrin; J718M71A7A / tetrachloroisophthalonitrile; S54S8B99E8 / Carbon Disulfide
  • [Other-IDs] NLM/ PMC2710931
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41. Iwanaga M, Tagawa M, Tsukasaki K, Kamihira S, Tomonaga M: Prevalence of monoclonal gammopathy of undetermined significance: study of 52,802 persons in Nagasaki City, Japan. Mayo Clin Proc; 2007 Dec;82(12):1474-9
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Prevalence of monoclonal gammopathy of undetermined significance: study of 52,802 persons in Nagasaki City, Japan.
  • OBJECTIVE: To assess the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in a large Japanese population.
  • Age- and sex-specific prevalence rates of MGUS were calculated.
  • RESULTS: Monoclonal gammopathy of undetermined significance was identified in 1088 of the 52,781 study participants.
  • The overall prevalence of MGUS was 2.1% (95% confidence interval [CI], 1.9%-2.2%) in the total population screened and 2.4% (95% CI, 2.0%-2.6%) in those 50 years or older.
  • The heavy chain isotypes of immunoglobulin were IgG in 73.6% of patients, IgA in 17.7%, IgM in 7.5%, and oligoclonal gammopathies in 1.1%.
  • CONCLUSION: The prevalence of MGUS is lower in this Japanese population than that reported in Western countries among people older than 60 years, especially among women.

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  • [CommentIn] Mayo Clin Proc. 2008 May;83(5):601-2; author reply 602-3 [18452695.001]
  • [CommentIn] Mayo Clin Proc. 2007 Dec;82(12):1457-9 [18053450.001]
  • (PMID = 18053454.001).
  • [ISSN] 0025-6196
  • [Journal-full-title] Mayo Clinic proceedings
  • [ISO-abbreviation] Mayo Clin. Proc.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
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42. Scudla V, Budíková M, Pika T, Bacovský J, Minarík J, Heinzová V, Langová K: [The comparison of serum levels of selected biomarkers in monoclonal gammopathy of undetermined significance and multiple myeloma]. Cas Lek Cesk; 2009;148(7):315-22
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  • [Title] [The comparison of serum levels of selected biomarkers in monoclonal gammopathy of undetermined significance and multiple myeloma].
  • [Transliterated title] Srovnání sérových hladin vybraných biologických působků u monoklonální gamapatie nejistého významu a mnohocetného myelomu.
  • BACKGROUND: The aim of the study was the evaluation of serum levels of 12 selected biomarkers in monoclonal gammopathy of undetermined significance (MGUS) and in initial, asyptomatic phase of multiple myeloma, especially from the view of potential differentiation of these conditions in clinical practice.
  • METHODS AND RESULTS: Analyzed group of 268 individuals consisted of 89 individuals with MGUS and 179 patients with MM examined in time of diagnosis before treatment initiation.
  • Pearson's chi2-test and test according to Mann-Whitney were used for statistical evaluation (p < 0.05).
  • Wide statistic differences in serum levels of analyzed markers in MGUS vs. MM were detected in case of beta2-M, TK, ICTP, OPG, HGF and syndecan-1 (p < 0.0001), lower differences in case of VCAM-1, PINP and VEGF (p = 0.003, 0.001 and 0.04), and without difference in case of Fas.
  • Except for thymidinekinase (p = 0.014) and syndecan-1 (p = 0.001) was not detected statistically important contrast of measured values in MGUS individuals and in patients with initial, asymptomatic phase of MM (stage 1), but these markers cannot be used in clinical practice due to significant overlap of serum values.
  • RESULTS: Although the significant differences in 9 of 12 evaluated serum levels of selected biomarkers in groups of MGUS and MM were seen, the results revealed that these markers are unprofitable to bring discriminatory potential capable of being used to distinguish between MGUS and initial, asymptomatic phase of MM.
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Diagnosis, Differential. Female. Humans. Male. Middle Aged

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  • (PMID = 19642297.001).
  • [ISSN] 0008-7335
  • [Journal-full-title] Casopís lékar̆ů c̆eských
  • [ISO-abbreviation] Cas. Lek. Cesk.
  • [Language] cze
  • [Publication-type] Comparative Study; English Abstract; Journal Article
  • [Publication-country] Czech Republic
  • [Chemical-registry-number] 0 / Biomarkers
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43. Dizdar O, Erman M, Cankurtaran M, Halil M, Ulger Z, Yavuz BB, Ariogul S, Pinar A, Harputluoglu H, Kars A, Celik I: Lower bone mineral density in geriatric patients with monoclonal gammopathy of undetermined significance. Ann Hematol; 2008 Jan;87(1):57-60
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  • [Title] Lower bone mineral density in geriatric patients with monoclonal gammopathy of undetermined significance.
  • The aim of this study was to investigate the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in a geriatric population in Turkey and compare bone mineral densities and related laboratory parameters of MGUS patients with those who do not have MGUS.
  • Among 1,012 patients enrolled, monoclonal band was detected in serum samples of 22 patients (2.17%), most of which were IgG type.
  • The remaining 20 patients were diagnosed with MGUS (1.97%).
  • The clinical and laboratory parameters of patients with and without MGUS were mostly comparable; however, bone mineral density measurements of patients with MGUS were significantly lower than those without MGUS (p = 0.007).
  • We suggest evaluation of geriatric patients with MGUS for the presence of osteopenia/osteoporosis considering the high frequency observed in this study.

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  • (PMID = 17874101.001).
  • [ISSN] 1432-0584
  • [Journal-full-title] Annals of hematology
  • [ISO-abbreviation] Ann. Hematol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Germany
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44. Iwanaga M, Tagawa M, Tsukasaki K, Matsuo T, Yokota K, Miyazaki Y, Fukushima T, Hata T, Imaizumi Y, Imanishi D, Taguchi J, Momita S, Kamihira S, Tomonaga M: Relationship between monoclonal gammopathy of undetermined significance and radiation exposure in Nagasaki atomic bomb survivors. Blood; 2009 Feb 19;113(8):1639-50

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  • [Title] Relationship between monoclonal gammopathy of undetermined significance and radiation exposure in Nagasaki atomic bomb survivors.
  • Radiation exposure is a possible predisposing factor for monoclonal gammopathy of undetermined significance (MGUS), but the association has been uncertain.
  • We investigated the relationship between radiation exposure and MGUS prevalence by using data from the M-protein screening for Nagasaki atomic bomb survivors between 1988 and 2004.
  • A total of 1082 cases of MGUS were identified from 52 525 participants.
  • MGUS prevalence was significantly higher in people exposed at distance within 1.5 km than beyond 3.0 km (PR, 1.4; 95% CI, 1.1-1.9) among those exposed at age 20 years or younger, but it was not found among those exposed at age 20 years or older.
  • MGUS prevalence was also significantly higher in people exposed to more than 0.1 Gy than those exposed to less than 0.01 Gy (PR, 1.7; 95% CI, 1.0-2.8) among those exposed at age 20 years or younger.
  • Thus, people exposed at younger age exhibited a significantly high risk of MGUS when exposed to a high radiation dose.
  • There was no clear association between radiation exposure and the malignant progression of MGUS.

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  • [CommentIn] Blood. 2009 Feb 19;113(8):1616-7 [19228928.001]
  • (PMID = 18849487.001).
  • [ISSN] 1528-0020
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
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45. Landgren O, Weiss BM: Patterns of monoclonal gammopathy of undetermined significance and multiple myeloma in various ethnic/racial groups: support for genetic factors in pathogenesis. Leukemia; 2009 Oct;23(10):1691-7
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  • [Title] Patterns of monoclonal gammopathy of undetermined significance and multiple myeloma in various ethnic/racial groups: support for genetic factors in pathogenesis.
  • Monoclonal gammopathy of undetermined significance (MGUS) is one of the most common premalignant disorders in Western countries.
  • Recent studies show that almost every multiple myeloma (MM) case is preceded by an MGUS stage.
  • Interestingly, prevalence and incidence patterns for MGUS and MM show striking disparity patterns across ethnic/racial groups, most notably the two- to threefold increase in both these disorders in African Americans compared with Caucasians.
  • In contrast, studies on Asian patients show lower prevalence/incidence for MGUS/MM compared with Caucasians.
  • Familial aggregation for both MGUS and MM has been observed; the risk for MGUS or MM in family members with these disorders is increased about two- to three fold compared with the general population.
  • Although underlying mechanisms remain unclear, there is evidence of heterogeneity among MGUS patients from different ethnic/racial groups.
  • For example, compared with Caucasians, African-American and African MGUS patients have reportedly lower rates of immunoglobulin M (IgM) MGUS (versus IgG/IgA MGUS) and higher rates of unquantifiable immunoglobulins (Igs).
  • This review focuses on racial disparity and familial aggregation patterns for MGUS and MM and discusses how these observations provide novel clues with regard to pathogenesis.

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  • (PMID = 19587704.001).
  • [ISSN] 1476-5551
  • [Journal-full-title] Leukemia
  • [ISO-abbreviation] Leukemia
  • [Language] eng
  • [Grant] United States / Intramural NIH HHS / /
  • [Publication-type] Journal Article; Research Support, N.I.H., Intramural; Review
  • [Publication-country] England
  • [Number-of-references] 61
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46. Bouvard B, Royer M, Chappard D, Audran M, Hoppé E, Legrand E: Monoclonal gammopathy of undetermined significance, multiple myeloma, and osteoporosis. Joint Bone Spine; 2010 Mar;77(2):120-4
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  • [Title] Monoclonal gammopathy of undetermined significance, multiple myeloma, and osteoporosis.
  • The finding of monoclonal gammopathy of undetermined significance (MGUS) is not infrequent during an evaluation for osteoporosis or a fracture.
  • In most cases, the diagnosis is MGUS, whose prevalence increases with age.
  • Although the impact of MGUS on bone mineral density, bone remodeling, and the fracture risk remains unclear, this asymptomatic hematological disorder may constitute a risk factor for osteoporosis.
  • Furthermore, each year, 1% of patients with MGUS progress to multiple myeloma, a disease whose pathophysiology and association with bone loss and pathological fractures are increasingly well understood.
  • Here, we discuss the pathophysiology of myeloma and MGUS and their impact in terms of bone mineral density, osteoporotic fractures, and bone turnover markers.
  • [MeSH-minor] Disease Progression. Fractures, Bone / epidemiology. Fractures, Bone / physiopathology. Humans. Prevalence

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  • [Copyright] Copyright 2009 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.
  • (PMID = 20097594.001).
  • [ISSN] 1778-7254
  • [Journal-full-title] Joint, bone, spine : revue du rhumatisme
  • [ISO-abbreviation] Joint Bone Spine
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] France
  • [Number-of-references] 46
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47. Mailankody S, Mena E, Yuan CM, Balakumaran A, Kuehl WM, Landgren O: Molecular and biologic markers of progression in monoclonal gammopathy of undetermined significance to multiple myeloma. Leuk Lymphoma; 2010 Dec;51(12):2159-70
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  • [Title] Molecular and biologic markers of progression in monoclonal gammopathy of undetermined significance to multiple myeloma.
  • Multiple myeloma (MM) is a malignant plasma cell dyscrasia localized in the bone marrow.
  • Recent studies have shown that MM is preceded in virtually all cases by a premalignant state called monoclonal gammopathy of undetermined significance (MGUS).
  • This review focuses on non-IgM MGUS and its progression to MM.
  • Although certain clinical markers of MGUS progression have been identified, it currently is not possible to accurately determine individual risk of progression.
  • A better understanding of the pathogenesis will allow us to define the biological high-risk precursor disease and, ultimately, to develop early intervention strategies designed to delay and prevent full-blown MM.
  • [MeSH-major] Biomarkers, Tumor / physiology. Monoclonal Gammopathy of Undetermined Significance / diagnosis. Monoclonal Gammopathy of Undetermined Significance / pathology. Multiple Myeloma / diagnosis
  • [MeSH-minor] Cytogenetic Analysis / methods. Disease Progression. Genomics / methods. Humans. Molecular Diagnostic Techniques. Precancerous Conditions / diagnosis. Precancerous Conditions / genetics. Precancerous Conditions / metabolism. Precancerous Conditions / pathology. Prognosis

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  • (PMID = 20958231.001).
  • [ISSN] 1029-2403
  • [Journal-full-title] Leukemia & lymphoma
  • [ISO-abbreviation] Leuk. Lymphoma
  • [Language] eng
  • [Grant] United States / Intramural NIH HHS / /
  • [Publication-type] Journal Article; Research Support, N.I.H., Intramural; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Biomarkers, Tumor
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48. Bergón E, Miravalles E, Bergón E, Miranda I, Bergón M: The predictive power of serum kappa/lambda ratios for discrimination between monoclonal gammopathy of undetermined significance and multiple myeloma. Clin Chem Lab Med; 2005;43(1):32-7
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  • [Title] The predictive power of serum kappa/lambda ratios for discrimination between monoclonal gammopathy of undetermined significance and multiple myeloma.
  • The predictive power of serum kappa/lambda ratios on initial presentation of immunoglobulin G (IgG) or IgA monoclonal component was studied to differentiate between monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) patients.
  • The retrospective study involved 145 patients clinically diagnosed with monoclonal gammopathy of undetermined significance or multiple myeloma, who had serum M-protein IgG <35 g/L or IgA <20 g/L at M-protein detection.
  • MM patients were considered as diseased and MGUS patients as non-diseased in order to estimate the performance characteristics of serum kappa/lambda ratios.
  • There was a statistically significant difference in kappa/lambda ratios distribution between both groups of patients, in both M-protein kappa-type (Mann-Whitney U=168, p<0.001) and in M-protein lambda-type (Mann-Whitney U=143, p<0.001).
  • Negative likelihood ratios at threshold levels of 0.6 and 4.2 were 2.17- and 3.32-fold greater, respectively, than positive likelihood ratios, so that the predictive power of a serum kappa/lambda ratio within these limits is better in ruling out (negative predictive power) than ruling in disease (positive predictive power).
  • The post-test characteristics of a serum kappa/lambda ratio interval between 0.6 and 4.2 in discriminating MGUS from MM in our geographic population were: sensitivity 0.96 (0.93-0.99 95% CI); specificity 0.70 (0.63-0.77); positive predictive value 0.68 (0.64-0.73); negative predictive value 0.96 (0.94-0.99); likelihood ratios (+)LR 3.23 (2.68-4.04); and (-)LR 17.16 (11.00-63.00).
  • Thus, serum M-protein with a kappa/lambda ratio between 0.6 and 4.2 increases the posterior probability of MGUS from 0.60 to 0.96 in asymptomatic patients, for whom only monitoring may be suggested when the serum kappa/lambda ratio is within these limits.

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  • [ErratumIn] Clin Chem Lab Med. 2005;43(3):349
  • (PMID = 15653439.001).
  • [ISSN] 1434-6621
  • [Journal-full-title] Clinical chemistry and laboratory medicine
  • [ISO-abbreviation] Clin. Chem. Lab. Med.
  • [Language] ENG
  • [Publication-type] Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Immunoglobulin G; 0 / Immunoglobulin M; 0 / Immunoglobulin kappa-Chains; 0 / Immunoglobulin lambda-Chains; 0 / Myeloma Proteins; 0 / multiple myeloma M-proteins
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49. Landgren O, Rajkumar SV, Pfeiffer RM, Kyle RA, Katzmann JA, Dispenzieri A, Cai Q, Goldin LR, Caporaso NE, Fraumeni JF, Blot WJ, Signorello LB: Obesity is associated with an increased risk of monoclonal gammopathy of undetermined significance among black and white women. Blood; 2010 Aug 19;116(7):1056-9
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  • [Title] Obesity is associated with an increased risk of monoclonal gammopathy of undetermined significance among black and white women.
  • The association of obesity with monoclonal gammopathy of undetermined significance (MGUS) is unknown.
  • Further, it is not known whether the increased risk of multiple myeloma and MGUS in blacks is related to socioeconomic status, genetic susceptibility, or both.
  • We screened 1000 black and 996 white women (range, 40-79 years) of similar socioeconomic status for MGUS; the aim of the study was to assess MGUS risk in relation to obesity and race.
  • A total of 39 (3.9%) blacks and 21 (2.1%) whites had MGUS.
  • On multivariate analysis, obesity (odds ratio [OR] = 1.8; P = .04), black race (OR = 1.8; P = .04), and increasing age (> 55 vs < 43 years; OR = 2.5; P = .03) were independently associated with an excess risk of MGUS.
  • The 2-fold excess of MGUS among blacks compared with whites of similar socioeconomic status supports a role for susceptibility genes in MGUS.

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  • [CommentIn] Blood. 2010 Aug 19;116(7):1020-1 [20724546.001]
  • (PMID = 20421448.001).
  • [ISSN] 1528-0020
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / P01 CA062242; United States / NCI NIH HHS / CA / P30 CA068485; United States / NCI NIH HHS / CA / R01 CA092447; United States / NCI NIH HHS / CA / R01 CA107476
  • [Publication-type] Comparative Study; Journal Article; Randomized Controlled Trial
  • [Publication-country] United States
  • [Other-IDs] NLM/ PMC2938127
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50. Skrtić A, Korać P, Krišto DR, Ajduković Stojisavljević R, Ivanković D, Dominis M: Immunohistochemical analysis of NOTCH1 and JAGGED1 expression in multiple myeloma and monoclonal gammopathy of undetermined significance. Hum Pathol; 2010 Dec;41(12):1702-10
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  • [Title] Immunohistochemical analysis of NOTCH1 and JAGGED1 expression in multiple myeloma and monoclonal gammopathy of undetermined significance.
  • Notch signaling is implicated in the pathogenesis of multiple myeloma expressing high level of active Notch proteins NOTCH1 and JAGGED1 in tumor plasma cells.
  • We investigated expression of NOTCH1 and JAGGED1 in bone marrow trephine biopsies of 80 newly diagnosed multiple myeloma and 20 monoclonal gammopathy of undetermined significance patients using immunohistochemical methods.
  • In contrast, both markers were negative in all monoclonal gammopathy of undetermined significance cases.
  • However, upon progression of disease from monoclonal gammopathy of undetermined significance to multiple myeloma (seen in 4 patients), analysis of the subsequent bone marrow biopsy showed weak expression of both markers in tumorous plasma cells.
  • Immunohistochemistry results were compared with the pattern of bone marrow infiltration, plasma cell differentiation, and the presence of t(11;14)(q13,q32), t(14;16)(q32;q23),and t(4;14)(p16.3;q23) and overall survival in multiple myeloma patients.
  • A significant correlation was found between strong NOTCH1 staining in multiple myeloma plasma cells and the diffuse type of bone marrow infiltration (P = .002) and an immature morphologic type of plasma cells (P = .043).
  • In conclusion, our results indicate importance of NOTCH1 and JAGGED1 expression in plasma cell neoplasia and a possible diagnostic value of their immunohistochemical evaluation of bone marrow infiltrates for multiple myeloma.
  • [MeSH-major] Calcium-Binding Proteins / metabolism. Intercellular Signaling Peptides and Proteins / metabolism. Membrane Proteins / metabolism. Monoclonal Gammopathy of Undetermined Significance / metabolism. Multiple Myeloma / metabolism. Receptor, Notch1 / metabolism
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Biomarkers, Tumor / metabolism. Croatia / epidemiology. Female. Humans. Male. Middle Aged. Plasma Cells / metabolism. Plasma Cells / pathology. Survival Rate

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  • [Copyright] Copyright © 2010 Elsevier Inc. All rights reserved.
  • (PMID = 20800871.001).
  • [ISSN] 1532-8392
  • [Journal-full-title] Human pathology
  • [ISO-abbreviation] Hum. Pathol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / Calcium-Binding Proteins; 0 / Intercellular Signaling Peptides and Proteins; 0 / Membrane Proteins; 0 / NOTCH1 protein, human; 0 / Receptor, Notch1; 134324-36-0 / Serrate proteins
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51. Stanganelli C, Arbelbide J, Fantl DB, Corrado C, Slavutsky I: DNA methylation analysis of tumor suppressor genes in monoclonal gammopathy of undetermined significance. Ann Hematol; 2010 Feb;89(2):191-9
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  • [Title] DNA methylation analysis of tumor suppressor genes in monoclonal gammopathy of undetermined significance.
  • Monoclonal gammopathy of undetermined significance (MGUS) is believed to be a precursor of multiple myeloma (MM).
  • We have analyzed methylation status of p15 INK4B , p16 INK4A , ARF, SOCS-1, p27 KIP1 , RASSF1A, and TP73 genes in bone marrow DNA samples from 21 MGUS and 44 MM patients, in order to determine the role of aberrant promoter methylation as one of the steps involved in the progression of MGUS to MM.
  • SOCS-1 gene methylation was significantly more frequent in MM (52%) than in MGUS (14%; p=0,006).
  • Methylation frequencies of TP73, ARF, p15 INK4B , p16 INK4A , and RASSF1A were comparable in MGUS: 33%, 29%, 29%, 5%, and 0%, to that observed in MM: 45%, 29%, 32%, 7%, and 2%.
  • The mean methylation index of MGUS was lower (0.16) than that of MM (0.24; p<0.05).
  • Correlations with clinicopathologic characteristics showed a higher mean age in MGUS patients with SOCS-1 methylated (p<0.001); meanwhile in MM, methylation of p15 INK4B was more frequent in males (p=0.009) and IgG isotype (p=0.038).
  • Our findings suggest methylation of TP73, ARF, p15 INK4B , and p16 INK4A as early events in the pathogenesis and development of plasma cell disorders; meanwhile, SOCS-1 methylation would be an important step in the clonal evolution from MGUS to MM.
  • [MeSH-major] DNA Methylation / physiology. Monoclonal Gammopathy of Undetermined Significance / genetics. Tumor Suppressor Proteins / genetics

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  • (PMID = 19727727.001).
  • [ISSN] 1432-0584
  • [Journal-full-title] Annals of hematology
  • [ISO-abbreviation] Ann. Hematol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Cyclin-Dependent Kinase Inhibitor p15; 0 / Cyclin-Dependent Kinase Inhibitor p16; 0 / DNA-Binding Proteins; 0 / Nuclear Proteins; 0 / RASSF1 protein, human; 0 / Tumor Suppressor Proteins; 0 / tumor suppressor protein p73; EC 3.6.5.2 / ADP-Ribosylation Factors
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52. Wang XW, Li F: [Clinical significance of monoclonal gammopathy with undetermined significance--review]. Zhongguo Shi Yan Xue Ye Xue Za Zhi; 2010 Oct;18(5):1365-9

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] [Clinical significance of monoclonal gammopathy with undetermined significance--review].
  • Monoclonal gammopathy with undetermined significance (MGUS) is the most common plasma cell disorder, MGUS is an asymptomatic premalignant disorder, which is markedly underdiagnosed in the general population.
  • The risk frequency of progression to multiple myeloma or a closely related plasma cell disorder was developed at a rate of 1.5% per year, indicating that the condition is not entirely benign.
  • As compared with control populations, the progression rate of MGUS into multiple myeloma, Waldenstr m's macroglobulinemia, AL amyloidosis and lymphoma were increased by 25, 46, 8.4 and 2.4 times respectively.
  • Numerous reports suggest an association of MGUS with a wide variety of other malignant and nonmalignant diseases.
  • The determining highest risk factors of progression, delaying or preventing the progression of MGUS, targeting at the highest risk of progression and improving overall quality of life, all of them are the current hot topics to be explored and summarized in this review.

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  • (PMID = 21129295.001).
  • [ISSN] 1009-2137
  • [Journal-full-title] Zhongguo shi yan xue ye xue za zhi
  • [ISO-abbreviation] Zhongguo Shi Yan Xue Ye Xue Za Zhi
  • [Language] CHI
  • [Publication-type] English Abstract; Journal Article; Review
  • [Publication-country] China
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53. Kristinsson SY, Fears TR, Gridley G, Turesson I, Mellqvist UH, Björkholm M, Landgren O: Deep vein thrombosis after monoclonal gammopathy of undetermined significance and multiple myeloma. Blood; 2008 Nov 1;112(9):3582-6
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Deep vein thrombosis after monoclonal gammopathy of undetermined significance and multiple myeloma.
  • Recently, 2 small hospital-based studies observed persons with the MM precursor condition, monoclonal gammopathy of undetermined significance (MGUS), to be at increased risk of developing DVT.
  • Among 4 196 197 veterans hospitalized at least once at US Veterans Affairs hospitals, we identified a total of 2374 cases of MGUS, and 39 272 persons were diagnosed with DVT (crude incidence 0.9 per 1000 person-years).
  • A total of 31 and 151 DVTs occurred among MGUS and MM patients, respectively (crude incidence 3.1 and 8.7 per 1000 person-years, respectively; P < .01).
  • Compared with the entire study population, the relative risk (RR) of DVT after a diagnosis of MGUS and MM was 3.3 (95% confidence interval [CI], 2.3-4.7) and 9.2 (95% CI, 7.9-10.8), respectively.
  • The most prominent excess risk of DVT was found during the first year after diagnosis of MGUS (RR = 8.4; 95% CI, 5.7-12.2) and MM (RR = 11.6; 95% CI, 9.2-14.5).
  • Among 229 MGUS cases (9.5%) that progressed to MM, only one person had a DVT diagnosis before transformation.
  • Our findings suggest the operation of shared underlying mechanisms causing coagulation abnormalities among patients with MGUS and MM.

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  • [CommentIn] Blood. 2008 Nov 1;112(9):3533 [18948581.001]
  • (PMID = 18559977.001).
  • [ISSN] 1528-0020
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] ENG
  • [Grant] United States / Intramural NIH HHS / /
  • [Publication-type] Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Other-IDs] NLM/ PMC2572787
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54. Madan S, Greipp PR: The incidental monoclonal protein: current approach to management of monoclonal gammopathy of undetermined significance (MGUS). Blood Rev; 2009 Nov;23(6):257-65

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] The incidental monoclonal protein: current approach to management of monoclonal gammopathy of undetermined significance (MGUS).
  • 'Monoclonal gammopathy of undetermined significance' (MGUS) is a pre-malignant disorder characterized by limited clonal proliferation of the bone marrow plasma cells without any evidence of end-organ damage.
  • A better understanding of the prevalence rates, natural history, and the risk factors for progression of MGUS, provides further insight into the clinical approach to management of this condition.
  • The clinical implications of MGUS such as the risk of fracture, miscellaneous conditions associated with a monoclonal M-protein, and a practical approach to the management of MGUS patients based on a risk-stratification model are discussed in this review.
  • [MeSH-major] Glycoproteins / blood. Monoclonal Gammopathy of Undetermined Significance / physiopathology. Monoclonal Gammopathy of Undetermined Significance / therapy

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  • (PMID = 19699016.001).
  • [ISSN] 1532-1681
  • [Journal-full-title] Blood reviews
  • [ISO-abbreviation] Blood Rev.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA 62242
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Glycoproteins; 0 / protein M (glycoprotein)
  • [Number-of-references] 128
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55. Horstman AL, Serck SL, Go RS: Macrocytosis associated with monoclonal gammopathy. Eur J Haematol; 2005 Aug;75(2):146-9

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Macrocytosis associated with monoclonal gammopathy.
  • OBJECTIVE: To report the potential association between unexplained macrocytosis and monoclonal gammopathy.
  • METHODS: We retrospectively reviewed the medical records of patients who had monoclonal protein detected by serum electrophoresis and immunofixation from October 1999 until September 2003 at our institution.
  • We collected data on patient demographics, evaluations performed for macrocytosis, pertinent laboratory tests relevant to the diagnosis of monoclonal gammopathy and presence of associated hematologic disorders.
  • RESULTS: We identified 258 patients with monoclonal gammopathy.
  • Of the latter group, 14 (5%) patients had no identifiable cause of macrocytosis after thorough evaluation and were considered to have macrocytosis associated with monoclonal gammopathy.
  • The median values for mean cell volume and serum monoclonal protein were 103.9 fL (range 100.8-109.8) and 1.95 gm/dL (range 0.8-4.3), respectively.
  • No correlation was found between the level of serum monoclonal protein and the degree of macrocytosis (r = +0.48, P = 0.08).
  • CONCLUSION: Macrocytosis can be a manifestation of monoclonal gammopathy.
  • Disorders associated with monoclonal gammopathy should be considered in the differential diagnoses during evaluation of macrocytosis.
  • [MeSH-minor] Aged. Aged, 80 and over. Bone Marrow Examination. Cell Size. Erythroid Precursor Cells. Female. Follow-Up Studies. Humans. Immunoglobulin G. Immunoglobulin Light Chains. Male. Middle Aged. Prevalence. Retrospective Studies

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  • [Copyright] Copyright Blackwell Munksgaard 2005.
  • (PMID = 16000131.001).
  • [ISSN] 0902-4441
  • [Journal-full-title] European journal of haematology
  • [ISO-abbreviation] Eur. J. Haematol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Denmark
  • [Chemical-registry-number] 0 / Immunoglobulin G; 0 / Immunoglobulin Light Chains
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56. Dietzfelbinger H: [Monoclonal gammopathy--multiple myeloma]. MMW Fortschr Med; 2005 Jun 16;147(24):32-3, 35-6
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] [Monoclonal gammopathy--multiple myeloma].
  • [Transliterated title] Monoklonale Gammopathie und Multiples Myelom. Vom Zufallsbefund zur lebensbedrohlichen Erkrankung.
  • The diagnosis of monoclonal gammopathy of undetermined significance (MGUS), requires both the detection of monoclonal gammopathy by immunofixation on the one hand, and the exclusion of signs of multiple myeloma (MM) on the other.
  • The risk of an MGUS evolving into an MM is about 1% per year.
  • The diagnosis of MM is established on the basis of a constellation of major and minor criteria that includes characteristic results of serum and urine electrophoresis and immunofixation, routine lab and bone marrow (plasma cell infiltration) studies as well as complications (anemia, renal failure, hypercalcemia, osteolysis).
  • Improved results have been achieved with high-dose chemotherapy plus various forms of stem cell transplantation.
  • [MeSH-major] Multiple Myeloma / diagnosis. Paraproteinemias / diagnosis
  • [MeSH-minor] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Chromosome Deletion. Chromosomes, Human, Pair 13. Early Diagnosis. Humans. Neoplasm Staging. Palliative Care. Prognosis. Stem Cell Transplantation

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  • (PMID = 16001531.001).
  • [ISSN] 1438-3276
  • [Journal-full-title] MMW Fortschritte der Medizin
  • [ISO-abbreviation] MMW Fortschr Med
  • [Language] ger
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] Germany
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57. Decaux O, Avet-Loiseau H, Grosbois B: [Malignant transformation of monoclonal gammopathy of undetermined significance]. Presse Med; 2007 Dec;36(12 Pt 3):1985-96

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] [Malignant transformation of monoclonal gammopathy of undetermined significance].
  • [Transliterated title] Transformation maligne des gammapathies monoclonales de signification indéterminée.
  • Monoclonal gammopathy of undetermined significance (MGUS) is found in approximately 3% of the general population aged 50 years or older.
  • MGUS is a premalignant state.
  • Some factors predictive of malignant transformation have been identified: type of serum monoclonal protein, monoclonal protein value, bone marrow plasmocytosis and serum free light chain ratio.
  • [MeSH-minor] Adult. Age Factors. Aged. Aged, 80 and over. Bone Marrow / pathology. Cell Transformation, Neoplastic. Cohort Studies. Diagnosis, Differential. Female. Follow-Up Studies. Genetic Markers. Humans. Immunoglobulin A / immunology. Immunoglobulin G / immunology. Immunoglobulin Isotypes. Immunoglobulin M / immunology. Leukemia, Lymphocytic, Chronic, B-Cell / etiology. Lymphoma, Non-Hodgkin / diagnosis. Lymphoma, Non-Hodgkin / etiology. Lymphoma, Non-Hodgkin / immunology. Male. Middle Aged. Multiple Myeloma / diagnosis. Multiple Myeloma / etiology. Multiple Myeloma / immunology. Multiple Myeloma / pathology. Myelography. Plasma Cells. Predictive Value of Tests. Retrospective Studies. Risk Factors. Time Factors. Waldenstrom Macroglobulinemia / diagnosis. Waldenstrom Macroglobulinemia / immunology. Waldenstrom Macroglobulinemia / pathology

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  • (PMID = 17509811.001).
  • [ISSN] 0755-4982
  • [Journal-full-title] Presse medicale (Paris, France : 1983)
  • [ISO-abbreviation] Presse Med
  • [Language] fre
  • [Publication-type] Comparative Study; English Abstract; Journal Article; Review
  • [Publication-country] France
  • [Chemical-registry-number] 0 / Genetic Markers; 0 / Immunoglobulin A; 0 / Immunoglobulin G; 0 / Immunoglobulin Isotypes; 0 / Immunoglobulin M
  • [Number-of-references] 61
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58. Hashimoto T, Arakawa K, Ohta Y, Suehiro T, Uesugi N, Nakayama M, Tsuchihashi T: Acquired fanconi syndrome with osteomalacia secondary to monoclonal gammopathy of undetermined significance. Intern Med; 2007;46(5):241-5
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  • [Title] Acquired fanconi syndrome with osteomalacia secondary to monoclonal gammopathy of undetermined significance.
  • Further exploration revealed monoclonal gammopathy of undetermined significance (MGUS) excreting urinary Bence Jones protein (kappa light chain).
  • Renal biopsy showed non-specific tubulointerstitial nephritis, yet neither crystalline inclusions in the cytoplasm of the tubular epithelium nor myeloma casts nor amyloid deposits were found.
  • MGUS was observed without chemotherapy.

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  • (PMID = 17329920.001).
  • [ISSN] 1349-7235
  • [Journal-full-title] Internal medicine (Tokyo, Japan)
  • [ISO-abbreviation] Intern. Med.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Alkalies; 0 / Immunoglobulin kappa-Chains; 0 / Phosphates; 1406-16-2 / Vitamin D; 9006-99-9 / Bence Jones Protein
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59. Panero J, Arbelbide J, Fantl DB, Rivello HG, Kohan D, Slavutsky I: Altered mRNA expression of telomere-associated genes in monoclonal gammopathy of undetermined significance and multiple myeloma. Mol Med; 2010 Nov-Dec;16(11-12):471-8
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Altered mRNA expression of telomere-associated genes in monoclonal gammopathy of undetermined significance and multiple myeloma.
  • In this study, we explored changes in the expression of the telomere maintenance genes, TRF1, TRF2 and TANK1 in patients with monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM).
  • Bone marrow (BM) samples from 132 patients, 64 with MGUS and 68 with MM, were studied.
  • MGUS patients showed increased TRF1 levels (P = 0.006) and lower expression of TRF2 (P = 0.005) and TANK1 (P = 0.003) compared with MM patients.
  • We observed increasing expression of TRF2 and TANK1 from GI to GIII in MGUS and MM, with differences for both genes in MM (P < 0.01) and for TRF2 in MGUS (P < 0.01).
  • Our findings provide the first evidence of a modification in the expression of telomeric proteins in plasma cell disorders, and suggest that mechanisms other than telomerase activation are involved in TL maintenance in these pathologies.

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  • (PMID = 20644899.001).
  • [ISSN] 1528-3658
  • [Journal-full-title] Molecular medicine (Cambridge, Mass.)
  • [ISO-abbreviation] Mol. Med.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / RNA, Messenger; 0 / TERF2 protein, human; 0 / Telomeric Repeat Binding Protein 1; 0 / Telomeric Repeat Binding Protein 2; EC 2.4.2.30 / Tankyrases; EC 2.4.4.30 / TNKS protein, human; EC 2.7.7.49 / Telomerase
  • [Other-IDs] NLM/ PMC2972391
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60. Kyle RA, Rajkumar SV: Monoclonal gammopathy of undetermined significance and smouldering multiple myeloma: emphasis on risk factors for progression. Br J Haematol; 2007 Dec;139(5):730-43
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Monoclonal gammopathy of undetermined significance and smouldering multiple myeloma: emphasis on risk factors for progression.
  • Monoclonal gammopathy of undetermined significance (MGUS) is characterized by a serum monoclonal protein <30 g/l, <10% plasma cells in the bone marrow, and absence of end-organ damage (CRAB-hypercalcaemia, renal insufficiency, anaemia, or bone lesions).
  • MGUS is present in 3% of persons >50 years and in 5% >70 years of age.
  • The risk of progression to multiple myeloma (MM) or a related disorder is 1% per year.
  • Patients with risk factors consisting of an abnormal serum free light chain ratio, non-immunoglobulin G (IgG) MGUS, and an elevated serum M protein >/=15 g/l had a risk of progression at 20 years of 58%, compared with 37% with two risk factors present, 21% with one risk factor present, and 5% when none of the risk factors were present.
  • Smouldering (asymptomatic) multiple myeloma is characterized by having a serum IgG or IgA monoclonal protein of 30 g/l or higher and/or 10% or more plasma cells in the bone marrow but no evidence of end-organ damage.
  • [MeSH-major] Monoclonal Gammopathy of Undetermined Significance / etiology. Multiple Myeloma / etiology
  • [MeSH-minor] Diagnosis, Differential. Disease Progression. Humans. Prevalence. Risk Factors

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  • [CommentIn] Br J Haematol. 2007 Dec;139(5):687-9 [18021082.001]
  • (PMID = 18021088.001).
  • [ISSN] 1365-2141
  • [Journal-full-title] British journal of haematology
  • [ISO-abbreviation] Br. J. Haematol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Number-of-references] 84
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61. Saad T, Agmon-Levin N, Shoenfeld Y: [Chronic stimulation of the immune system in sarcoidosis and monoclonal gammopathy of undetermined significance]. Harefuah; 2009 Dec;148(12):809-10, 857, 856
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] [Chronic stimulation of the immune system in sarcoidosis and monoclonal gammopathy of undetermined significance].
  • Sarcoidosis is a systemic granulomatous disease which predominantly involves the lungs.
  • Monoclonal gammopathy of undetermined significance (MGUS) characterized by clonal proliferation of plasma cells, can develop into multiple myeloma at a later stage.
  • Although the cause of sarcoidosis remains unknown, the most likely etiology relates to chronic stimulation of the immune system that may result in polyclonal B cell proliferation.
  • In some patients this polyclonal proliferation may develop into a monoclonal B-cell proliferation and induce the appearance of monoclonal gammopathy.
  • In this article, a possible linkage between sarcoidosis and MGUS is raised, based on the case study of a 67-year-old woman and a review of the literature.

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  • (PMID = 20088430.001).
  • [ISSN] 0017-7768
  • [Journal-full-title] Harefuah
  • [ISO-abbreviation] Harefuah
  • [Language] heb
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] Israel
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62. Sethi S, Sukov WR, Zhang Y, Fervenza FC, Lager DJ, Miller DV, Cornell LD, Krishnan SG, Smith RJ: Dense deposit disease associated with monoclonal gammopathy of undetermined significance. Am J Kidney Dis; 2010 Nov;56(5):977-82
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Dense deposit disease associated with monoclonal gammopathy of undetermined significance.
  • Dense deposit disease (DDD) is a rare glomerular disease that typically affects children, young adults, and much less commonly, older patients.
  • Since 1995, we have diagnosed DDD in 14 patients aged 49 years or older; 10 of these patients (71.4%) carry a concomitant diagnosis of monoclonal gammopathy of undetermined significance (MGUS).
  • In aggregate, these findings suggest that in some adults with MGUS, DDD may develop as a result of autoantibodies to factor H (or other complement proteins) that on a permissive genetic background (the H402 allele of factor H) lead to dysregulation of the AP with subsequent glomerular damage.
  • Thus, DDD in some older patients may be a distinct clinicopathologic entity that represents an uncommon complication of MGUS.

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  • [Copyright] Copyright © 2010 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
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  • (PMID = 20832153.001).
  • [ISSN] 1523-6838
  • [Journal-full-title] American journal of kidney diseases : the official journal of the National Kidney Foundation
  • [ISO-abbreviation] Am. J. Kidney Dis.
  • [Language] ENG
  • [Grant] United States / NIDDK NIH HHS / DK / R01 DK074409; United States / NIDDK NIH HHS / DK / R01 DK074409-05; United States / NIDDK NIH HHS / DK / DK074409
  • [Publication-type] Case Reports; Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Autoantibodies; 80295-65-4 / Complement Factor H
  • [Other-IDs] NLM/ NIHMS233036; NLM/ PMC3970198
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63. Ali YM, Urowitz MB, Ibanez D, Gladman DD: Monoclonal gammopathy in systemic lupus erythematosus. Lupus; 2007;16(6):426-9
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  • [Title] Monoclonal gammopathy in systemic lupus erythematosus.
  • We studied the prevalence, type and associated features of monoclonal gammopathy in patients with systemic lupus erythematosus (SLE).
  • Monoclonal gammopathy patients were matched with two controls each from the same database by age at SLE diagnosis, sex and disease duration.
  • Of 1083 patients followed at the Lupus Clinic 59 (5.4%) were identified with monoclonal gammopathy.
  • The gammopathies included 32 with IgG, 14 IgM and 12 IgA, one undefined.
  • Nine (15.3%) malignancies were detected in monoclonal gammopathy and 12 (10.1%) in the controls during the entire course of their disease (P = 0.13).
  • There was no difference between patients with monoclonal gammopathy and their controls with respect to disease activity, damage, or dose of steroids.
  • The mean ESR and gammaglobulin levels in the monoclonal gammopathy patients were higher than the controls at last visit.
  • We conclude that monoclonal gammopathy is more frequent in SLE patients than in the general population and has a benign course in patients with SLE.
  • There were no differences in disease manifestations, treatment approaches, or malignancies between SLE patients with and those without monoclonal gammopathy.
  • [MeSH-major] Lupus Erythematosus, Systemic / complications. Monoclonal Gammopathy of Undetermined Significance / etiology

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  • (PMID = 17664233.001).
  • [ISSN] 0961-2033
  • [Journal-full-title] Lupus
  • [ISO-abbreviation] Lupus
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Immunoglobulin A; 0 / Immunoglobulin G; 0 / Immunoglobulin M; 0 / gamma-Globulins
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64. Kumar S, Rajkumar SV, Kyle RA, Lacy MQ, Dispenzieri A, Fonseca R, Lust JA, Gertz MA, Greipp PR, Witzig TE: Prognostic value of circulating plasma cells in monoclonal gammopathy of undetermined significance. J Clin Oncol; 2005 Aug 20;23(24):5668-74
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  • [Title] Prognostic value of circulating plasma cells in monoclonal gammopathy of undetermined significance.
  • PURPOSE: Monoclonal gammopathy of undetermined significance (MGUS) progresses to multiple myeloma or another related plasma cell disorder (PCD) at a rate of approximately 1% per year.
  • Identification of patients with MGUS at high risk of progression will allow development of preventive strategies.
  • We studied the prognostic value of circulating plasma cells (PCs) in patients with MGUS to predict progression.
  • PATIENTS AND METHODS: Patients were eligible for this retrospective analysis if they were seen at the Mayo Clinic between 1984 and 1997, were diagnosed with MGUS, and had an analysis of the peripheral blood for circulating PCs by the slide-based immunofluorescence method.
  • Other factors with prognostic value were high levels of M protein and non-immunoglobulin G heavy-chain type.
  • CONCLUSION: The presence of circulating PCs, especially when combined with other known prognostic factors such as M protein concentration and immunoglobulin isotype, identify a group of individuals with MGUS at higher risk of progression to overt multiple myeloma.
  • [MeSH-major] Multiple Myeloma / immunology. Paraproteinemias / immunology. Plasma Cells / immunology
  • [MeSH-minor] Adolescent. Child. Child, Preschool. Disease Progression. Female. Humans. Immunoglobulin M / immunology. Infant. Male. Myeloma Proteins / immunology. Prognosis. Retrospective Studies. Survival Analysis

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  • (PMID = 16110026.001).
  • [ISSN] 0732-183X
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA100080; United States / NCI NIH HHS / CA / CA62242; United States / NCI NIH HHS / CA / CA65125; United States / NCI NIH HHS / CA / CA85818; United States / NCI NIH HHS / CA / CA93842
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Immunoglobulin M; 0 / Myeloma Proteins; 0 / multiple myeloma M-proteins
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65. Varettoni M, Corso A, Cocito F, Mangiacavalli S, Pascutto C, Zappasodi P, Pica G, Lazzarino M: Changing pattern of presentation in monoclonal gammopathy of undetermined significance: a single-center experience with 1400 patients. Medicine (Baltimore); 2010 Jul;89(4):211-6
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  • [Title] Changing pattern of presentation in monoclonal gammopathy of undetermined significance: a single-center experience with 1400 patients.
  • To assess whether the pattern of presentation and the outcome of monoclonal gammopathy of undetermined significance (MGUS) have changed over the last 3 decades, we evaluated 1400 patients, divided into 3 groups: group I (1975-1987), group II (1988-1997), and group III (1998-2007).
  • We observed a significant increase in age (p = 0.001), IgM and biclonal MGUS (p = 0.003), hemoglobin (p < 0.0001), and albumin (p = 0.0001), and a significant reduction of monoclonal (M)-protein concentration (p < 0.0001), percentage of bone marrow plasma cells (p < 0.0001), and beta2-microglobulin (p = 0.0001) over the 3 decades.
  • The proportion of patients with M-protein <1.5 g/dL was significantly higher in group III (66%) than in group II (44%) and group I (26%) (p < 0.0001).
  • Patients with M-protein <1.5 g/dL had the same life expectancy as the general population (standardized mortality ratio 1.09; p = 0.41).
  • In conclusion, we found that the pattern of presentation of MGUS has changed over time and now includes a higher proportion of patients with more favorable presenting features and probably a better outcome compared to patients presenting in the past.
  • This changing scenario calls for revising the current concepts of the clinical significance of MGUS and the management of patients.
  • [MeSH-minor] Adult. Age Distribution. Aged. Aged, 80 and over. Disease Progression. Female. Humans. Male. Middle Aged. Prevalence. Retrospective Studies. Risk Factors

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  • (PMID = 20616660.001).
  • [ISSN] 1536-5964
  • [Journal-full-title] Medicine
  • [ISO-abbreviation] Medicine (Baltimore)
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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66. Brown LM, Gridley G, Check D, Landgren O: Risk of multiple myeloma and monoclonal gammopathy of undetermined significance among white and black male United States veterans with prior autoimmune, infectious, inflammatory, and allergic disorders. Blood; 2008 Apr 1;111(7):3388-94
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  • [Title] Risk of multiple myeloma and monoclonal gammopathy of undetermined significance among white and black male United States veterans with prior autoimmune, infectious, inflammatory, and allergic disorders.
  • In a retrospective cohort of more than 4 million white and black male United States (US) veterans, we explored the role of specific prior autoimmune, infectious, inflammatory, and allergic disorders in the etiology of multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS).
  • The analysis included 4641 patients (3040 white, 1601 black) and 2046 patients (1312 white; 734 black) with a discharge diagnosis of MM and MGUS, respectively.
  • Using Poisson regression, we calculated age-adjusted relative risks (RRs) and 95% confidence intervals (CIs) for the relationship between MM, MGUS, and specific prior medical conditions.
  • Risks for MGUS were generally of similar magnitude.
  • Our results indicate that various types of immune-mediated conditions might act as triggers for MM/MGUS development.

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  • (PMID = 18239085.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] ENG
  • [Grant] United States / Intramural NIH HHS / /
  • [Publication-type] Journal Article; Multicenter Study; Research Support, N.I.H., Intramural
  • [Publication-country] United States
  • [Other-IDs] NLM/ PMC2275008
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67. Pepe J, Petrucci MT, Mascia ML, Piemonte S, Fassino V, Romagnoli E, Minisola S: The effects of alendronate treatment in osteoporotic patients affected by monoclonal gammopathy of undetermined significance. Calcif Tissue Int; 2008 Jun;82(6):418-26
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  • [Title] The effects of alendronate treatment in osteoporotic patients affected by monoclonal gammopathy of undetermined significance.
  • In patients with monoclonal gammopathy of undetermined significance (MGUS) the increase of bone turnover rate can increase the risk of fracture.
  • We studied 100 patients affected by MGUS, grouped according to the presence (group A, 50 patients) or absence (group B) of vertebral fractures and/or osteoporosis.
  • In the nine patients of this group not taking alendronate, BMD values of the lumbar spine and total femur decreased by 1.6% (P < or = 0.001 ) and 1.3% (P < or = 0.01), respectively.
  • At 18 months we observed significant decreases of serum bone markers: the difference between the groups was -23.2 (P < or = 0.01) for bone alkaline phosphatase, -23.6 for osteocalcin (P < or = 0.01), -35.1 for C-terminal telopeptides of collagen type I (P < or = 0.001), and -0.47 for bone sialoprotein (P = nonsignificant).
  • Treatment with alendronate could lead to a significant reduction in fracture risk in MGUS patients with skeletal fragility.
  • [MeSH-major] Alendronate / therapeutic use. Bone Density Conservation Agents / therapeutic use. Monoclonal Gammopathy of Undetermined Significance / drug therapy. Osteoporosis, Postmenopausal / drug therapy

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  • (PMID = 18528609.001).
  • [ISSN] 0171-967X
  • [Journal-full-title] Calcified tissue international
  • [ISO-abbreviation] Calcif. Tissue Int.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Biomarkers; 0 / Bone Density Conservation Agents; 0 / Calcium, Dietary; 0 / Collagen Type I; 0 / Peptides; 0 / collagen type I trimeric cross-linked peptide; 104982-03-8 / Osteocalcin; 106441-73-0 / Osteopontin; 1C6V77QF41 / Cholecalciferol; EC 3.1.3.1 / Alkaline Phosphatase; X1J18R4W8P / Alendronate
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68. Wadhera RK, Rajkumar SV: Prevalence of monoclonal gammopathy of undetermined significance: a systematic review. Mayo Clin Proc; 2010 Oct;85(10):933-42
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  • [Title] Prevalence of monoclonal gammopathy of undetermined significance: a systematic review.
  • Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma cell disorder that is associated with a lifelong risk of multiple myeloma.
  • We conducted a systematic review of all studies investigating the prevalence and incidence of MGUS in the online database PubMed.
  • The following MeSH search headings were used: monoclonal gammopathy, benign and prevalence; monoclonal gammopathy, benign and incidence; paraproteinemia and prevalence; and paraproteinemia and incidence.
  • Fourteen studies that met prespecified criteria were included and systematically assessed to identify the most accurate prevalence estimates of MGUS based on age, sex, and race.
  • On the basis of our systematic review, we estimate that the crude prevalence of MGUS in those older than 50 years is 3.2% in a predominantly white population.
  • Additionally, MGUS is significantly more prevalent in black people (5.9%-8.4%) than in white people (3.0%-3.6%).
  • We conclude that MGUS is a common premalignant plasma cell disorder in the general population of those older than 50 years.

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  • (PMID = 20713974.001).
  • [ISSN] 1942-5546
  • [Journal-full-title] Mayo Clinic proceedings
  • [ISO-abbreviation] Mayo Clin. Proc.
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / P01 CA062242; United States / NCI NIH HHS / CA / R01 CA107476; United States / NCI NIH HHS / CA / CA107476; United States / NCI NIH HHS / CA / CA62242
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Review
  • [Publication-country] England
  • [Other-IDs] NLM/ PMC2947966
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69. Martín MG, Romero Colás MS, Dourdil Sahún MV, Olave P, Alba PR, Banzo JB: BaselinTc99-MIBI scanning predicts survival in multiple myeloma and helps to differentiate this disease from monoclonal gammopathy of unknown significance. Haematologica; 2005 Aug;90(8):1141-3
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  • [Title] BaselinTc99-MIBI scanning predicts survival in multiple myeloma and helps to differentiate this disease from monoclonal gammopathy of unknown significance.
  • We performed baselineTc(99)-MIBI scanning in 43 patients with multiple myeloma (MM) and in 31 with monoclonal gammopathy of unknown significance (MGUS) patients.
  • MGUS patients had normal or very low scores.
  • [MeSH-minor] Diagnosis, Differential. Humans. Predictive Value of Tests. Radiopharmaceuticals. Survival Analysis

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  • (PMID = 16079119.001).
  • [ISSN] 1592-8721
  • [Journal-full-title] Haematologica
  • [ISO-abbreviation] Haematologica
  • [Language] eng
  • [Publication-type] Letter
  • [Publication-country] Italy
  • [Chemical-registry-number] 0 / Radiopharmaceuticals; 971Z4W1S09 / Technetium Tc 99m Sestamibi
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70. Rossi D, De Paoli L, Franceschetti S, Capello D, Vendramin C, Lunghi M, Conconi A, Magnani C, Gaidano G: Prevalence and clinical characteristics of immune thrombocytopenic purpura in a cohort of monoclonal gammopathy of uncertain significance. Br J Haematol; 2007 Jul;138(2):249-52
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Prevalence and clinical characteristics of immune thrombocytopenic purpura in a cohort of monoclonal gammopathy of uncertain significance.
  • Monoclonal gammopathy of uncertain significance (MGUS) may become symptomatic for autoimmune manifestations.
  • We report on the prevalence and clinical course of immune thrombocytopenic purpura (ITP) observed in a consecutive series of 228 MGUS patients.
  • At MGUS diagnosis, ITP was determined in 6/228 cases, accounting for a prevalence of 2630/100 000 [95% confidence interval (CI): 1210-5620].
  • After a follow-up of 681.3 patient-years, the crude incidence of ITP in MGUS was 146.8 per 100 000 patient-year (95% CI: 3.7-817.8).
  • Overall, these observations point to an association between MGUS and ITP.
  • [MeSH-major] Monoclonal Gammopathy of Undetermined Significance / complications. Purpura, Thrombocytopenic, Idiopathic / complications

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  • (PMID = 17535272.001).
  • [ISSN] 0007-1048
  • [Journal-full-title] British journal of haematology
  • [ISO-abbreviation] Br. J. Haematol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Anti-Inflammatory Agents; 0 / Immunosuppressive Agents; 8N3DW7272P / Cyclophosphamide; VB0R961HZT / Prednisone
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71. Sharma V, Agarwal MP, Giri S: Monoclonal gammopathy associated with visceral leishmaniasis. Braz J Infect Dis; 2010 May-Jun;14(3):297-8
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  • [Title] Monoclonal gammopathy associated with visceral leishmaniasis.
  • Monoclonal gammopathy can accompany diverse conditions and is usually benign.
  • It should be distinguished from monoclonal gammopathy of undetermined significance (MGUS) which can rarely turn malignant.
  • Visceral leishmaniasis has only rarely been associated with monoclonal gammopathy.
  • We describe the case of a 55-year-old male who had monoclonal gammopathy associated with visceral leishmanisais, which reversed with stibogluconate therapy.

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  • (PMID = 20835517.001).
  • [ISSN] 1678-4391
  • [Journal-full-title] The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases
  • [ISO-abbreviation] Braz J Infect Dis
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Brazil
  • [Chemical-registry-number] 0 / Antiprotozoal Agents; V083S0159D / Antimony Sodium Gluconate
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72. Konstantinopoulos PA, Pantanowitz L, Dezube BJ: Higher prevalence of monoclonal gammopathy of undetermined significance in African Americans than whites--the unknown role of underlying HIV infection. J Natl Med Assoc; 2006 Nov;98(11):1860-1
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  • [Title] Higher prevalence of monoclonal gammopathy of undetermined significance in African Americans than whites--the unknown role of underlying HIV infection.
  • The age-adjusted prevalence rate of monoclonal gammopathy of undetermined significance (MGUS) is three-fold higher in African Americans than whites.
  • Since the risk of progression of MGUS to MM is equal in both races, identification of exogenous and genetic risk factors of MGUS [such as genetic pre-disposition; diet; and chronic antigenic exposure related to sexually transmitted diseases, including human immunodeficiency virus (HIV) infection] is essential for unraveling the etiology of the racial disparity for MM.
  • HIV infection, a well-documented risk factor for MGUS, is more frequent in African-American patients.
  • Future epidemiologic studies dealing with plasma cell disorders should carefully examine the relationship between race, HIV infection status, prevalence of MGUS and its ultimate progression to MM.
  • [MeSH-minor] Disease Progression. European Continental Ancestry Group / statistics & numerical data. Humans. Multiple Myeloma / virology. Prevalence

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  • [Cites] Blood. 2006 Feb 1;107(3):904-6 [16210333.001]
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  • (PMID = 17128699.001).
  • [ISSN] 1943-4693
  • [Journal-full-title] Journal of the National Medical Association
  • [ISO-abbreviation] J Natl Med Assoc
  • [Language] eng
  • [Publication-type] Editorial
  • [Publication-country] United States
  • [Other-IDs] NLM/ PMC2569800
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73. Bacher U, Haferlach T, Kern W, Alpermann T, Schnittger S, Haferlach C: Correlation of cytomorphology, immunophenotyping, and interphase fluorescence in situ hybridization in 381 patients with monoclonal gammopathy of undetermined significance and 301 patients with plasma cell myeloma. Cancer Genet Cytogenet; 2010 Dec;203(2):169-75
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  • [Title] Correlation of cytomorphology, immunophenotyping, and interphase fluorescence in situ hybridization in 381 patients with monoclonal gammopathy of undetermined significance and 301 patients with plasma cell myeloma.
  • To further clarify the transformation from monoclonal gammopathy of undetermined significance (MGUS) to plasma cell myeloma (PCM), we compared interphase fluorescence in situ hybridization (FISH) patterns in 381 MGUS and 301 PCM patients.
  • According to the World Health Organization and the International Myeloma Working Group, a threshold of 10% of bone marrow plasma cells separated MGUS from PCM.
  • After magnetic activated cell sorting for CD138(+) cells, FISH succeeded in 272 of 301 (90.4%) PCM, but in only 302 of 381 (79.3%) MGUS cases (P < 0.001).
  • Cytogenetic alterations were more frequent in PCM (237 of 272; 87.1%) than MGUS (169 of 302; 56.0%; P = 0.0002).
  • PCM showed a median of two cytogenetic alterations (range, 0-9) and MGUS one (range, 0-6).
  • Considering only cases with a yield of plasma cells allowing five or more FISH probes, del(13)(q14) was found in 99 of 251 (39.3%) PCM but in only 59 of 267 (22.1%) MGUS (P = 0.0001), del(17p) in 15 PCM (6.0%) and in 6 MGUS (2.2%) patients (P = 0.029).
  • A t(4;14)/IGH-FGFR3 was detected in 28 PCM (11.1%) and 5 MGUS (1.9%; P < 0.001).
  • Cytomorphology detected higher numbers of plasma cells than multiparameter flow cytometry (median ratio 4.25).
  • This study underlines the genetic heterogeneity of MGUS similar to PCM.
  • Genetic analysis might contribute to more diversified monitoring strategies for MGUS patients.
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Cell Separation. Chromosome Deletion. Cytogenetic Analysis. Cytogenetics. Female. Flow Cytometry / methods. Humans. Immunophenotyping. Male. Middle Aged. Models, Genetic. Syndecan-1 / biosynthesis

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  • [Copyright] Copyright © 2010 Elsevier Inc. All rights reserved.
  • (PMID = 21156229.001).
  • [ISSN] 1873-4456
  • [Journal-full-title] Cancer genetics and cytogenetics
  • [ISO-abbreviation] Cancer Genet. Cytogenet.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Syndecan-1
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74. Kyle RA, Benson J, Larson D, Therneau T, Dispenzieri A, Melton Iii LJ, Rajkumar SV: IgM monoclonal gammopathy of undetermined significance and smoldering Waldenström's macroglobulinemia. Clin Lymphoma Myeloma; 2009 Mar;9(1):17-8
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  • [Title] IgM monoclonal gammopathy of undetermined significance and smoldering Waldenström's macroglobulinemia.
  • Immunoglobulin M monoclonal gammopathy of undetermined significance (IgM-MUS) was diagnosed in 213 Mayo Clinic patients who were residents of 11 counties in southeastern Minnesota from 1960 to 1994.
  • During long-term follow-up, 29 (14%) developed non-Hodgkin lymphoma (n = 17), Waldenström's macroglobulinemia (WM; n = 6), chronic lymphocytic leukemia (n = 3), and AL amyloidosis (n = 3) with relative risks of 15-, 262-, 6-, and 16-fold, respectively.
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Disease Progression. Female. Follow-Up Studies. Humans. Male. Middle Aged. Minnesota / epidemiology. Multivariate Analysis. Young Adult

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  • (PMID = 19362962.001).
  • [ISSN] 1557-9190
  • [Journal-full-title] Clinical lymphoma & myeloma
  • [ISO-abbreviation] Clin Lymphoma Myeloma
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / R01 CA107476
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Immunoglobulin M
  • [Other-IDs] NLM/ NIHMS498185; NLM/ PMC3773469
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75. Batuecas Mohedano M, Carballo Alvarez F, García Menéndez L: [Follow-up of serum monoclonal gammopathy at Guadalajara Health Area]. An Med Interna; 2006 Dec;23(12):569-72

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] [Follow-up of serum monoclonal gammopathy at Guadalajara Health Area].
  • [Transliterated title] Seguimiento de una cohorte de pacientes con gammapatía monoclonal sérica en el Area Sanitaria de Guadalajara.
  • OBJECTIVE: To study the clinical course of patients with a serum monoclonal protein at Guadalajara Health Area.
  • MATERIAL AND METHODS: Prospective study of 186 patients with a newly diagnosed monoclonal component.
  • RESULTS: The cumulative transformation probability at 43 months was 4.99% for those patients whose monoclonal gammopathy was overlooked, and 2% at 23 months for patients with monoclonal gammopathy of undetermined significance.
  • The conditional mortality rate (patients/months) at 4 years due to haematological disease was 4.48 x 10(-4) for overlooked patients, 0 for diagnosed of monoclonal gammopathy of undetermined significance and 1.388 x 10(-2) for multiple myeloma diagnosed.
  • DISCUSSION: A non malignant M component must be followed up due to it could increase patients survival rate in relation with transformation in malignant disease.

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  • (PMID = 17371143.001).
  • [ISSN] 0212-7199
  • [Journal-full-title] Anales de medicina interna (Madrid, Spain : 1984)
  • [ISO-abbreviation] An Med Interna
  • [Language] spa
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] Spain
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76. Keller CE, Hays AP, Rowland LP, Moghadaszadeh B, Beggs AH, Bhagat G: Adult-onset nemaline myopathy and monoclonal gammopathy. Arch Neurol; 2006 Jan;63(1):132-4
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  • [Title] Adult-onset nemaline myopathy and monoclonal gammopathy.
  • He also had a monoclonal gammopathy.
  • This is the fifth report of adult-onset nemaline myopathy in a patient with monoclonal gammopathy, suggesting that the occurrence of these entities may be more than a chance association.

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  • (PMID = 16401746.001).
  • [ISSN] 0003-9942
  • [Journal-full-title] Archives of neurology
  • [ISO-abbreviation] Arch. Neurol.
  • [Language] eng
  • [Grant] United States / NIAMS NIH HHS / AR / AR44345
  • [Publication-type] Case Reports; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
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77. Berenson JR, Yellin O, Boccia RV, Flam M, Wong SF, Batuman O, Moezi MM, Woytowitz D, Duvivier H, Nassir Y, Swift RA: Zoledronic acid markedly improves bone mineral density for patients with monoclonal gammopathy of undetermined significance and bone loss. Clin Cancer Res; 2008 Oct 1;14(19):6289-95
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Zoledronic acid markedly improves bone mineral density for patients with monoclonal gammopathy of undetermined significance and bone loss.
  • PURPOSE: Patients with monoclonal gammopathy of undetermined significance (MGUS) have increased rates of bone resorption, osteopenia, osteoporosis, and risk of fractures.
  • This study was undertaken to determine the efficacy and safety of zoledronic acid for patients with MGUS and enhanced bone loss.
  • EXPERIMENTAL DESIGN: In this phase II open-label study, 54 patients with MGUS and osteopenia or osteoporosis were administered zoledronic acid 4 mg i.v. at 0, 6, and 12 months.
  • RESULTS: At study end for all patients (N = 54), L-spine T-scores improved by a median of +0.27 (range, -0.38 to +3.91), corresponding to a median increase in bone mineral density of +15.0% (range, -18.0% to +1,140.0%; P < 0.0001).
  • CONCLUSIONS: Zoledronic acid administered i.v. at a dosage of 4 mg every 6 months for three doses total was well-tolerated and substantially improved bone mineral density for patients with MGUS and bone loss.
  • [MeSH-major] Bone Density. Bone Density Conservation Agents / pharmacology. Bone Diseases / drug therapy. Diphosphonates / pharmacology. Imidazoles / pharmacology. Monoclonal Gammopathy of Undetermined Significance / drug therapy

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  • (PMID = 18829511.001).
  • [ISSN] 1078-0432
  • [Journal-full-title] Clinical cancer research : an official journal of the American Association for Cancer Research
  • [ISO-abbreviation] Clin. Cancer Res.
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase I; Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Bone Density Conservation Agents; 0 / Diphosphonates; 0 / Imidazoles; 6XC1PAD3KF / zoledronic acid
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78. Papadaki HA, Pontikoglou C, Stavroulaki E, Minadakis G, Eliopoulos DA, Pyrovolaki K, Skordilis P, Eliopoulos GD: High prevalence of Helicobacter pylori infection and monoclonal gammopathy of undetermined significance in patients with chronic idiopathic neutropenia. Ann Hematol; 2005 May;84(5):317-20
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  • [Title] High prevalence of Helicobacter pylori infection and monoclonal gammopathy of undetermined significance in patients with chronic idiopathic neutropenia.
  • The prevalence of Helicobacter pylori infection was evaluated in 120 patients with chronic idiopathic neutropenia (CIN), 8 patients with monoclonal gammopathy of undetermined significance (MGUS) associated with CIN, and 74 age- and sex-matched normal volunteers, all derived from the same geographical area.
  • The purpose of the study was to investigate the possible causal relationships of H. pylori infection with the development of MGUS in CIN patients.
  • We found that the prevalence of H. pylori infection was elevated to 69.2% in the group of CIN patients, 100% in the group of patients with CIN-associated MGUS, and 32.4% in the group of control subjects.
  • No statistically significant difference, however, was found in the prevalence of H. pylori infection between CIN patients with concomitant MGUS and CIN patients without MGUS, no resolution of the gammopathy after eradication of the bacterium, no significant rise in the titers of serum anti-H. pylori antibodies, and no formation of an abnormal precipitation line in immunoelectrophoresis using a saline extract of NCTC11367 H. pylori reference strain as antigen.
  • We concluded that there is no evidence that H. pylori infection is the cause of MGUS in CIN patients.

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  • (PMID = 15731921.001).
  • [ISSN] 0939-5555
  • [Journal-full-title] Annals of hematology
  • [ISO-abbreviation] Ann. Hematol.
  • [Language] eng
  • [Publication-type] Evaluation Studies; Journal Article
  • [Publication-country] Germany
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79. Schop RF, Van Wier SA, Xu R, Ghobrial I, Ahmann GJ, Greipp PR, Kyle RA, Dispenzieri A, Lacy MQ, Rajkumar SV, Gertz MA, Fonseca R: 6q deletion discriminates Waldenström macroglobulinemia from IgM monoclonal gammopathy of undetermined significance. Cancer Genet Cytogenet; 2006 Sep;169(2):150-3
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  • [Title] 6q deletion discriminates Waldenström macroglobulinemia from IgM monoclonal gammopathy of undetermined significance.
  • IgM monoclonal gammopathy of undetermined significance (IgM MGUS) and Waldenström macroglobulinemia (WM) are sometimes clinically difficult to distinguish.
  • To further clarify the area of minimal deletion at 6q (6q-) and to address the issue of whether 6q- occurs in IgM MGUS, 12 IgM MGUS and 38 WM patients were studied by fluorescence in situ hybridization using probes targeting different chromosomal segments of 6q.
  • No 6q deletions were found in IgM MGUS samples.
  • These results indicate that 6q- can distinguish WM from IgM MGUS and is likely to be a secondary event.

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  • (PMID = 16938573.001).
  • [ISSN] 0165-4608
  • [Journal-full-title] Cancer genetics and cytogenetics
  • [ISO-abbreviation] Cancer Genet. Cytogenet.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA21115-25C; United States / NCI NIH HHS / CA / P01 CA62242; United States / NCI NIH HHS / CA / R01 CA83724-01
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Immunoglobulin M
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80. Landgren O, Kristinsson SY, Goldin LR, Caporaso NE, Blimark C, Mellqvist UH, Wahlin A, Bjorkholm M, Turesson I: Risk of plasma cell and lymphoproliferative disorders among 14621 first-degree relatives of 4458 patients with monoclonal gammopathy of undetermined significance in Sweden. Blood; 2009 Jul 23;114(4):791-5
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  • [Title] Risk of plasma cell and lymphoproliferative disorders among 14621 first-degree relatives of 4458 patients with monoclonal gammopathy of undetermined significance in Sweden.
  • Familial clustering of the precursor condition, monoclonal gammopathy of undetermined significance (MGUS) has been observed in case reports and in smaller studies.
  • Using population-based data from Sweden, we identified 4458 MGUS patients, 17505 population-based controls, and first-degree relatives of patients (n = 14621) and controls (n = 58387) with the aim to assess risk of MGUS and lymphoproliferative malignancies among first-degree relatives of MGUS patients.
  • Compared with relatives of controls, relatives of MGUS patients had increased risk of MGUS (relative risk [RR] = 2.8; 1.4-5.6), multiple myeloma (MM; RR = 2.9; 1.9-4.3), lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM; RR = 4.0; 1.5-11), and chronic lymphocytic leukemia (CLL; RR = 2.0; 1.2-2.3).
  • Relatives of patients with IgG/IgA MGUS had a 4.0-fold (1.7-9.2), 2.9-fold (1.7-4.9), and 20-fold (2.3-170) elevated risk of developing MGUS, MM, and LPL/WM, respectively.
  • Relatives of IgM MGUS patients had 5.0-fold (1.1-23) increased CLL risk and nonsignificant excess MM and LPL/WM risks.
  • The results were very similar when we assessed risk by type of first-degree relative, age at MGUS (above/below 65 years), or sex.
  • Risk of non-Hodgkin lymphoma or Hodgkin lymphoma was not increased among MGUS relatives.
  • Among first-degree relatives of a nationwide MGUS cohort, we found elevated risks of MGUS, MM, LPL/WM, and CLL, supporting a role for germline susceptibility genes, shared environmental influences, or an interaction between both.


81. Sasaki H, Kato T, Murakami A, Nakayasu K, Yajima Y: [A case of monoclonal gammopathy with corneal stroma deposits]. Nippon Ganka Gakkai Zasshi; 2006 Apr;110(4):307-11
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  • [Title] [A case of monoclonal gammopathy with corneal stroma deposits].
  • BACKGROUND: Monoclonal gammopathy is a group of disorders characterized by proliferation of a single clone of plasma cells that produce monoclonal protein.
  • Sometimes benign monoclonal gammopathy that is a symptomatic can turn into a malignancy like multiple myeloma.
  • We present a case of monoclonal gammopathy with corneal deposits which was treated with deep lamellar keratoplasty (DLKP).
  • RESULTS: We diagnosed monoclonal gammopathy in a blood test that showed elevation of serum immunoglobulin G and the Kappa chain.
  • CONCLUSIONS: Corneal deposits of unknown origin might turn into monoclonal gammopathy that could be a life-threatening disease.
  • It is important for ophthalmologists to check the whole body of a patient when finding corneal deposits.
  • [MeSH-major] Corneal Diseases / complications. Corneal Stroma / pathology. Monoclonal Gammopathy of Undetermined Significance / complications

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  • (PMID = 16642949.001).
  • [ISSN] 0029-0203
  • [Journal-full-title] Nippon Ganka Gakkai zasshi
  • [ISO-abbreviation] Nippon Ganka Gakkai Zasshi
  • [Language] jpn
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] Japan
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82. Pepe J, Petrucci MT, Nofroni I, Fassino V, Diacinti D, Romagnoli E, Minisola S: Lumbar bone mineral density as the major factor determining increased prevalence of vertebral fractures in monoclonal gammopathy of undetermined significance. Br J Haematol; 2006 Sep;134(5):485-90
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  • [Title] Lumbar bone mineral density as the major factor determining increased prevalence of vertebral fractures in monoclonal gammopathy of undetermined significance.
  • The possible relationships between biochemical measurements and both densitometric and radiographic indexes of skeletal fragility were evaluated in 65 postmenopausal women with monoclonal gammopathy of undetermined significance (MGUS).
  • There was a significantly higher prevalence of vertebral fractures in the MGUS group compared with a control population (P < or = 0.001).
  • The MGUS patients were then grouped according to the presence or absence of at least one mild vertebral fracture.
  • Patients with fractures (Fx, n=34) were older (62.8 +/- 6.1 years), with long-standing disease (8.8 +/- 7.1 years) when compared with those without fractures (NFx, n=31; 59.7 +/- 5.0 years, P < or = 0.05 and 5.8 +/- 4.1 years, P < or = 0.05).
  • The receptor activator of nuclear factor kappa-B ligand/osteoprotegerin ratio was higher in Fx compared with NFx (0.092 +/- 0.018 vs. 0.082 +/- 0.020; P < or = 0.05).
  • Lumbar spine (0.811 +/- 0.14 vs. 0.956 +/- 0.12 g/cm2), femoral neck (0.660 +/- 0.09 vs. 0.747 +/- 0.10 g/cm2) and total bone mineral density (BMD) (0.788 +/- 0.11 vs. 0.884 +/- 0.11 g/cm2) were lower (all P < or = 0.001) in FxMGUS compared with Nfx patients.
  • This study provides an indication for the measurement of BMD in MGUS patients, as a means of predicting vertebral fractures, especially in those that are asymptomatic.
  • [MeSH-major] Bone Density. Lumbar Vertebrae. Monoclonal Gammopathy of Undetermined Significance / physiopathology. Spinal Fractures / physiopathology

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  • (PMID = 16848794.001).
  • [ISSN] 0007-1048
  • [Journal-full-title] British journal of haematology
  • [ISO-abbreviation] Br. J. Haematol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Biomarkers; 0 / Carrier Proteins; 0 / Glycoproteins; 0 / Membrane Glycoproteins; 0 / Osteoprotegerin; 0 / RANK Ligand; 0 / Receptor Activator of Nuclear Factor-kappa B; 0 / Receptors, Cytoplasmic and Nuclear; 0 / Receptors, Tumor Necrosis Factor; 0 / TNFRSF11A protein, human; 0 / TNFRSF11B protein, human; 0 / TNFSF11 protein, human
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83. Hartley MA, Sokol L, Caceres G, Hussein MA, List A, Pinilla-Ibarz J: Monoclonal gammopathy of undetermined significance disguised as chronic neutrophilic leukemia. Mediterr J Hematol Infect Dis; 2010;2(1):e2010002
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  • [Title] Monoclonal gammopathy of undetermined significance disguised as chronic neutrophilic leukemia.
  • We encountered a 60-year-old woman with a medical history of diabetes mellitus, osteoporosis, peripheral vascular disease, and hypertension who had earlier presented at an outside facility with knee pain, which led to a finding of elevated neutrophil count of 35×10(9)/L.
  • Because she was otherwise asymptomatic but continued showing elevated neutrophil levels, she sought a second opinion at our facility.
  • Serum protein immunoelectrophoresis with immunofixation revealed an immunoglobulin A (IgA)-κ monoclonal gammopathy concentration of 1305 mg/dL (normal 80-350 mg/dL) but relatively normal concentrations of IgG of 840 mg/dL (620-1400 mg/dL) and IgM of 36 mg/dL (45-250 mg/dL).
  • Using clonal analysis, we found a polyclonal expression pattern in all cell types analyzed.
  • We concluded that our patient's neutrophilia may have been due to the underlying monoclonal gammopathy.
  • This is the first case in the literature of a patient with monoclonal gammopathy of undetermined significance presenting with chronic neutrophilia, mimicking chronic neutrophilic leukemia (CNL).

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  • (PMID = 21415944.001).
  • [ISSN] 2035-3006
  • [Journal-full-title] Mediterranean journal of hematology and infectious diseases
  • [ISO-abbreviation] Mediterr J Hematol Infect Dis
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Italy
  • [Other-IDs] NLM/ PMC3033111
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84. Gregersen H, Sørensen HT, Engebjerg MC, Jensen P, Severinsen MT, Nørgaard M: Survival of cancer patients with prior monoclonal gammopathy of undetermined significance. Eur J Intern Med; 2010 Dec;21(6):564-8
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  • [Title] Survival of cancer patients with prior monoclonal gammopathy of undetermined significance.
  • INTRODUCTION: It is unknown whether a prior diagnosis of monoclonal gammopathy of undetermined significance (MGUS) affects cancer survival.
  • DESIGN AND METHODS: We linked data on 1652 cases of MGUS diagnosed during 1978-2006 in North Jutland County, Denmark with the Danish Cancer Registry and the National Patient Registry to obtain information on survival of cancer patients with a previous MGUS compared with that of cancer patients without MGUS, matched on cancer type, age, sex and year of diagnosis.
  • RESULTS: We included 323 cancer patients with previously detected MGUS and 3154 comparison cancer patients without MGUS.
  • The 5-year survival probability was 26.2% (95% CI, 21.2%-31.5%) in cancer patients with MGUS and 30.5% (28.8%-32.1%) in cancer patients without MGUS.
  • Survival following a diagnosis of multiple myeloma, the cancer site of main interest, did not differ according to a preceding MGUS diagnosis.
  • Among patients with immune-related cancers (liver, cervix, malignant melanoma and non-melanoma skin cancers), a preceding MGUS diagnosis was associated with reduced survival (adjusted MRR=1.49 (95% CI: 0.96-2.31)).
  • In contrast, for other non-haematological cancers a prior MGUS diagnosis was associated with a lower MRR (0.78 (95% CI, 0.63-0.96)).
  • CONCLUSION: Our study does not indicate that previously detected MGUS is a prognostic factor for cancer survival in general.
  • [MeSH-major] Monoclonal Gammopathy of Undetermined Significance / mortality. Multiple Myeloma / mortality. Neoplasms / mortality

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  • [Copyright] Copyright © 2010 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
  • (PMID = 21111946.001).
  • [ISSN] 1879-0828
  • [Journal-full-title] European journal of internal medicine
  • [ISO-abbreviation] Eur. J. Intern. Med.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Netherlands
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85. Kyle RA, Durie BG, Rajkumar SV, Landgren O, Blade J, Merlini G, Kröger N, Einsele H, Vesole DH, Dimopoulos M, San Miguel J, Avet-Loiseau H, Hajek R, Chen WM, Anderson KC, Ludwig H, Sonneveld P, Pavlovsky S, Palumbo A, Richardson PG, Barlogie B, Greipp P, Vescio R, Turesson I, Westin J, Boccadoro M, International Myeloma Working Group: Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management. Leukemia; 2010 Jun;24(6):1121-7
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  • [Title] Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management.
  • Monoclonal gammopathy of undetermined significance (MGUS) was identified in 3.2% of 21 463 residents of Olmsted County, Minnesota, 50 years of age or older.
  • The risk of progression to multiple myeloma, Waldenstrom's macroglobulinemia, AL amyloidosis or a lymphoproliferative disorder is approximately 1% per year.
  • Low-risk MGUS is characterized by having an M protein <15 g/l, IgG type and a normal free light chain (FLC) ratio.
  • Patients should be followed with serum protein electrophoresis at six months and, if stable, can be followed every 2-3 years or when symptoms suggestive of a plasma cell malignancy arise.
  • Patients with intermediate and high-risk MGUS should be followed in 6 months and then annually for life.
  • The risk of smoldering (asymptomatic) multiple myeloma (SMM) progressing to multiple myeloma or a related disorder is 10% per year for the first 5 years, 3% per year for the next 5 years and 1-2% per year for the next 10 years.
  • [MeSH-major] Monoclonal Gammopathy of Undetermined Significance / complications. Multiple Myeloma / etiology
  • [MeSH-minor] Disease Progression. Humans. Practice Guidelines as Topic. Prognosis. Risk Factors

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  • (PMID = 20410922.001).
  • [ISSN] 1476-5551
  • [Journal-full-title] Leukemia
  • [ISO-abbreviation] Leukemia
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Number-of-references] 23
  • [Investigator] Abonour R; Alexanian R; Anderson KC; Attal M; Avet-Loiseau H; Badros A; Barlogie B; Baris D; Batille R; Beksac M; Belch A; Bensinger B; Bergsagel PL; Bird J; Bladé J; Boccadoro M; Cavo M; Chanan-Khan A; Chen WM; Child T; Chim J; Chng WJ; Comenzo R; Crowley J; Dalton W; Davies F; de Souza C; Delforge M; Dimopoulos M; Dispenzieri A; Durie BG; Drach J; Einsele H; Facon T; Fantl D; Fermand JP; Fonseca R; Gahrton G; Garcia-Sanz R; Gasparetto C; Gertz M; Gibson J; Giralt S; Goldschmidt H; Greipp P; Hajek R; Hardan I; Harousseau JL; Hata H; Hattori Y; Heffner T; Ho J; Hungria V; Ida S; Jacobs P; Jagannath S; Jian H; Joshua D; Jurczyszyn A; Kawano M; Kröger N; Kumar S; Kyle RA; Lahuerta J; Landgren O; Laubach J; Lee JH; LeLeu X; Lentzsch S; Lokhorst H; Lonial S; Ludwig H; Maiolino A; Mateos M; Mehta J; Mellqvist UH; Merlini G; Mikhael J; Morales AR; Moreau P; Morgan G; Munshi N; Niesvizky R; Nouel A; Novis Y; Orlowski R; Palumbo A; Pavlovsky S; Pilarski L; Powles R; Rajkumar SV; Reece D; Reiman T; Richardson PG; Roodman D; Rosinol L; San Miguel J; Sezer O; Shah JJ; Shaughnessy J; Shimizu K; Shustik C; Siegel D; Singhal S; Sonneveld P; Spencer A; Stadtmauer E; Stewart K; Terpos E; Tosi P; Tricot G; Turesson I; Vanderkerken K; Van Ness B; Van Riet I; Vescio R; Vesole D; Waage A; Wang M; Weber D; Westin J; Wheatley K; Yehuda DB; Zonder J
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86. Kourou K, Suga Y, Muramatsu S, Yaguchi H, Ogawa H: A case of diffuse plane normolipemic xanthomatosis associated with pancytopenia and monoclonal gammopathy. J Dermatol; 2006 Jan;33(1):64-7
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  • [Title] A case of diffuse plane normolipemic xanthomatosis associated with pancytopenia and monoclonal gammopathy.
  • Laboratory investigations and bone marrow aspirate smears showed that our patient had myelodysplastic syndrome (MDS) associated with pancytopenia and monoclonal gammopathy of undetermined significance.
  • Because our patient had neither a malignant hematological disorder nor a severe systemic disease, monoclonal gammopathy might explain the pathogenesis of DPNX in the present case.
  • [MeSH-major] Monoclonal Gammopathy of Undetermined Significance / diagnosis. Pancytopenia / diagnosis. Skin Diseases / diagnosis. Xanthomatosis / diagnosis
  • [MeSH-minor] Aged. Axilla / pathology. Diagnosis, Differential. Humans. Male

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  • (PMID = 16469089.001).
  • [ISSN] 0385-2407
  • [Journal-full-title] The Journal of dermatology
  • [ISO-abbreviation] J. Dermatol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Japan
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87. Kovárová L, Michálek J, Kýr M, Penka M, Hájek R: [Comparison of dendritic cells antigens in healthy volunteers and monoclonal gammopathy of undetermined significance and/or multiple myeloma patients]. Klin Onkol; 2008;21(1):20-5
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  • [Title] [Comparison of dendritic cells antigens in healthy volunteers and monoclonal gammopathy of undetermined significance and/or multiple myeloma patients].
  • DESIGN AND SUBJECTS: Maturation of DCs from 10 healthy donors, 14 monoclonal gammopathy of undetermined significance patients and 14 multiple myeloma patients was tested in an in vitro study.
  • CONCLUSION: Under serum free conditions there was no difference between healthy volunteers, MGUS and patients, but CD40L stimulation did not lead to the full maturation ofDCs.

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  • (PMID = 19097411.001).
  • [ISSN] 0862-495X
  • [Journal-full-title] Klinická onkologie : casopis Ceské a Slovenské onkologické spolecnosti
  • [ISO-abbreviation] Klin Onkol
  • [Language] cze
  • [Publication-type] Comparative Study; English Abstract; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Czech Republic
  • [Chemical-registry-number] 0 / Antigens, Surface; 0 / Interleukin-6; 0 / Receptors, CCR; 147205-72-9 / CD40 Ligand
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88. Tancred TM, Belch AR, Reiman T, Pilarski LM, Kirshner J: Altered expression of fibronectin and collagens I and IV in multiple myeloma and monoclonal gammopathy of undetermined significance. J Histochem Cytochem; 2009 Mar;57(3):239-47
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  • [Title] Altered expression of fibronectin and collagens I and IV in multiple myeloma and monoclonal gammopathy of undetermined significance.
  • Multiple myeloma (MM) is an incurable B-cell malignancy that arises in the bone marrow (BM).
  • We analyzed the expression and localization of fibronectin, laminin, and collagens I and IV in the core biopsies of normal donors and patients with monoclonal gammopathy of undetermined significance (MGUS) or MM.
  • Expression of collagen IV in the BM of MGUS and MM patients was higher than in the BM from normal donors.
  • Compared with the plasma cells isolated from the patients with low- and mid-level plasmacytosis, sorted CD138(+) plasma cells from MM patients with high-level plasmacytosis overexpressed collagen IV.
  • Our findings show that, compared with normal controls, the ECM composition of the bone, endosteum, and BM is aberrant in patients with MM, further establishing ECM as a key player in the MM disease process.
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Bone Marrow / metabolism. Bone and Bones / metabolism. Extracellular Matrix / metabolism. Female. Humans. Male. Middle Aged. Plasma Cells / metabolism

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  • (PMID = 19001640.001).
  • [ISSN] 0022-1554
  • [Journal-full-title] The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society
  • [ISO-abbreviation] J. Histochem. Cytochem.
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Collagen Type I; 0 / Collagen Type IV; 0 / Fibronectins
  • [Other-IDs] NLM/ PMC2664936
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89. Berenson JR, Yellin O: Monoclonal gammopathy of undetermined significance: why identification of these patients and assessment of their skeletons is important. Clin Lymphoma Myeloma; 2009 Aug;9(4):311-5
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  • [Title] Monoclonal gammopathy of undetermined significance: why identification of these patients and assessment of their skeletons is important.
  • Monoclonal gammopathy of undetermined significance (MGUS) is a plasma cell disorder characterized by the presence of a serum monoclonal immunoglobulin (M-protein) at <or= 3 g/dL.
  • It is an asymptomatic premalignant disorder that can progress to multiple myeloma and related B-cell disorders.
  • Recent studies have suggested the association of MGUS with enhanced bone loss and debilitating skeletal complications, particularly vertebral compression fractures (VCFs) often leading to back pain.
  • Early identification of MGUS and evaluation of bone status will facilitate prophylactic treatment with bisphosphonates to increase bone density and likely reduce the risk of fractures as well as identify patients with VCFs who might benefit from early surgical intervention.
  • [MeSH-major] Fractures, Compression / diagnosis. Fractures, Compression / therapy. Monoclonal Gammopathy of Undetermined Significance / diagnosis. Monoclonal Gammopathy of Undetermined Significance / therapy. Multiple Myeloma / diagnosis. Multiple Myeloma / therapy
  • [MeSH-minor] Antibodies, Monoclonal / blood. Humans. Quality of Life. Risk Factors. Treatment Outcome

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  • (PMID = 19717382.001).
  • [ISSN] 1938-0712
  • [Journal-full-title] Clinical lymphoma & myeloma
  • [ISO-abbreviation] Clin Lymphoma Myeloma
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal
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90. Bida JP, Kyle RA, Therneau TM, Melton LJ 3rd, Plevak MF, Larson DR, Dispenzieri A, Katzmann JA, Rajkumar SV: Disease associations with monoclonal gammopathy of undetermined significance: a population-based study of 17,398 patients. Mayo Clin Proc; 2009 Aug;84(8):685-93
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  • [Title] Disease associations with monoclonal gammopathy of undetermined significance: a population-based study of 17,398 patients.
  • OBJECTIVE: To systematically study the association of monoclonal gammopathy of undetermined significance (MGUS) with all diseases in a population-based cohort of 17,398 patients, all of whom were uniformly tested for the presence or absence of MGUS.
  • Among 17,398 samples tested, 605 cases of MGUS and 16,793 negative controls were identified.
  • RESULTS: We confirmed a significant association in 14 (19%) of 75 previously reported disease associations with MGUS, including vertebral and hip fractures and osteoporosis.
  • Systematic analysis of all 16,062 diagnostic disease codes found additional previously unreported associations, including mycobacterium infection and superficial thrombophlebitis.
  • CONCLUSION: These results have major implications both for confirmed associations and for 61 diseases in which the association with MGUS is likely coincidental.

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  • (PMID = 19648385.001).
  • [ISSN] 1942-5546
  • [Journal-full-title] Mayo Clinic proceedings
  • [ISO-abbreviation] Mayo Clin. Proc.
  • [Language] ENG
  • [Grant] United States / NIAMS NIH HHS / AR / AR30582; United States / NCI NIH HHS / CA / P01 CA062242; United States / NIAMS NIH HHS / AR / R01 AR030582; United States / NCI NIH HHS / CA / R01 CA107476; United States / NCI NIH HHS / CA / CA107476; United States / NCI NIH HHS / CA / CA62242
  • [Publication-type] Comparative Study; Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] England
  • [Other-IDs] NLM/ PMC2719521
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91. Jang ST, Sohn IS, Jin ES, Cho JM, Kim CJ, Lim SJ: A case of cardiac dysfunction associated with monoclonal gammopathy of undetermined significance. J Korean Med Sci; 2009 Apr;24(2):354-6
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  • [Title] A case of cardiac dysfunction associated with monoclonal gammopathy of undetermined significance.
  • The monoclonal gammopathies (MG) are monoclonal neoplasms related to each other by virtue of their development from common progenitors in the B lymphocyte lineage.
  • Bone marrow (BM) studies and immunoelectrophoresis were compatible with monoclonal gammopathy of undetermined significance.
  • This is the case of non-amyloidotic light chain deposition cardiomyopathy.

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  • (PMID = 19399286.001).
  • [ISSN] 1598-6357
  • [Journal-full-title] Journal of Korean medical science
  • [ISO-abbreviation] J. Korean Med. Sci.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Korea (South)
  • [Chemical-registry-number] 0 / Immunoglobulin kappa-Chains
  • [Other-IDs] NLM/ PMC2672144
  • [Keywords] NOTNLM ; Echocardiography / Paraproteinemias / Ventricular Dysfunction
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92. Okura T, Miyoshi K, Nagao T, Jotoku M, Enomoto D, Irita J, Kurata M, Higaki J: Light chain deposition disease developing 15 years following the diagnosis of monoclonal gammopathy of undetermined significance. Intern Med; 2009;48(2):101-4
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  • [Title] Light chain deposition disease developing 15 years following the diagnosis of monoclonal gammopathy of undetermined significance.
  • Fifteen years previously she had been diagnosed with monoclonal gammopathy of undetermined significance (MGUS).
  • Her renal biopsy specimen revealed thickened basement membrane, mesangial cell proliferation and an increase in the mesangial matrix.
  • These findings confirmed a diagnosis of light chain deposit disease (LCDD) with MGUS.
  • The development of LCDD in patients with MGUS for fifteen years is very rare.

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  • (PMID = 19145054.001).
  • [ISSN] 1349-7235
  • [Journal-full-title] Internal medicine (Tokyo, Japan)
  • [ISO-abbreviation] Intern. Med.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Immunoglobulin A; 0 / Immunoglobulin kappa-Chains
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93. Vachon CM, Kyle RA, Therneau TM, Foreman BJ, Larson DR, Colby CL, Phelps TK, Dispenzieri A, Kumar SK, Katzmann JA, Rajkumar SV: Increased risk of monoclonal gammopathy in first-degree relatives of patients with multiple myeloma or monoclonal gammopathy of undetermined significance. Blood; 2009 Jul 23;114(4):785-90
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  • [Title] Increased risk of monoclonal gammopathy in first-degree relatives of patients with multiple myeloma or monoclonal gammopathy of undetermined significance.
  • We examined whether monoclonal gammopathy of undetermined significance (MGUS) is increased in first-degree relatives of multiple myeloma (MM) or MGUS patients.
  • Probands were recruited from a population-based prevalence study (MGUS) and the Mayo Clinic (MM).
  • The prevalence of MGUS in relatives was compared with population-based rates.
  • Nine-hundred eleven relatives of 232 MM and 97 MGUS probands were studied.
  • By electrophoresis, MGUS was detected in 55 (6%) relatives, and immunofixation identified 28 additional relatives for an age- and sex-adjusted prevalence of 8.1% (95% CI, 6.3 to 9.8).
  • The prevalence of MGUS in relatives increased with age (1.9%, 6.9%, 11.6%, 14.6%, 21.0% for ages 40-49, 50-59, 60-69, 70-79, >/= 80 years, respectively; P < .001).
  • Using similar MGUS detection methods, there was a higher risk of MGUS in relatives (age-adjusted risk ratio [RR], 2.6; 95% CI, 1.9 to 3.4) compared with the reference population.
  • The increased risk was seen among relatives of MM (RR, 2.0; 95% CI, 1.4 to 2.8) and MGUS probands (RR, 3.3; 95% CI, 2.1 to 4.8).
  • The increased risk of MGUS in first-degree relatives of MGUS or MM patients implies shared environment and/or genetics.

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  • (PMID = 19179466.001).
  • [ISSN] 1528-0020
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / P01 CA062242; United States / NCI NIH HHS / CA / R01 CA107476; United States / NCI NIH HHS / CA / CA107476; United States / NCI NIH HHS / CA / CA62242
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Immunoglobulin Isotypes; 0 / Immunoglobulins; 0 / M-proteins (Myeloma)
  • [Other-IDs] NLM/ PMC2716020
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94. Berenson JR, Anderson KC, Audell RA, Boccia RV, Coleman M, Dimopoulos MA, Drake MT, Fonseca R, Harousseau JL, Joshua D, Lonial S, Niesvizky R, Palumbo A, Roodman GD, San-Miguel JF, Singhal S, Weber DM, Zangari M, Wirtschafter E, Yellin O, Kyle RA: Monoclonal gammopathy of undetermined significance: a consensus statement. Br J Haematol; 2010 Jul;150(1):28-38
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  • [Title] Monoclonal gammopathy of undetermined significance: a consensus statement.
  • On February 25, 2009, a panel of international experts on plasma cell dyscrasia and skeletal disease met to discuss monoclonal gammopathy of undetermined significance (MGUS).
  • This non-malignant B-cell disorder is the most common plasma cell dyscrasia and is associated with an increased risk of developing serious B-cell disorders.
  • Individuals with MGUS also have an increased risk of osteoporosis and osteopenia associated with an increased likelihood of developing fractures especially in the vertebral column, peripheral neuropathy and thromboembolic events.
  • The goal of the meeting was to develop a consensus statement regarding the appropriate tests to screen, evaluate and follow-up patients with MGUS.
  • The panel also addressed the identification and treatment of MGUS-related skeletal problems, thromboembolic events and neurological complications.
  • The following consensus statement outlines the conclusions and marks the first time that a consensus statement for the screening and treatment of MGUS has been clearly stated.
  • [MeSH-major] Monoclonal Gammopathy of Undetermined Significance / diagnosis
  • [MeSH-minor] Aged. Bone Diseases, Metabolic / diagnosis. Bone Diseases, Metabolic / etiology. Cell Transformation, Neoplastic. Disease Progression. Humans. Long-Term Care / methods. Long-Term Care / standards. Mass Screening / methods. Mass Screening / organization & administration. Middle Aged. Peripheral Nervous System Diseases / drug therapy. Peripheral Nervous System Diseases / etiology. Prognosis. Risk Factors

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  • (PMID = 20507313.001).
  • [ISSN] 1365-2141
  • [Journal-full-title] British journal of haematology
  • [ISO-abbreviation] Br. J. Haematol.
  • [Language] eng
  • [Publication-type] Consensus Development Conference; Journal Article
  • [Publication-country] England
  • [Number-of-references] 86
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95. Spisek R, Kukreja A, Chen LC, Matthews P, Mazumder A, Vesole D, Jagannath S, Zebroski HA, Simpson AJ, Ritter G, Durie B, Crowley J, Shaughnessy JD Jr, Scanlan MJ, Gure AO, Barlogie B, Dhodapkar MV: Frequent and specific immunity to the embryonal stem cell-associated antigen SOX2 in patients with monoclonal gammopathy. J Exp Med; 2007 Apr 16;204(4):831-40
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  • [Title] Frequent and specific immunity to the embryonal stem cell-associated antigen SOX2 in patients with monoclonal gammopathy.
  • Specific targets of cellular immunity in human premalignancy are largely unknown.
  • Monoclonal gammopathy of undetermined significance (MGUS) represents a precursor lesion to myeloma (MM).
  • We show that antigenic targets of spontaneous immunity in MGUS differ from MM.
  • MGUS patients frequently mount a humoral and cellular immune response against SOX2, a gene critical for self-renewal in embryonal stem cells.
  • Intranuclear expression of SOX2 marks the clonogenic CD138(-) compartment in MGUS.
  • Cellular immunity to SOX2 inhibits the clonogenic growth of MGUS cells in vitro.
  • Detection of anti-SOX2 T cells predicts favorable clinical outcome in patients with asymptomatic plasmaproliferative disorders.

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  • (PMID = 17389240.001).
  • [ISSN] 0022-1007
  • [Journal-full-title] The Journal of experimental medicine
  • [ISO-abbreviation] J. Exp. Med.
  • [Language] ENG
  • [Grant] United States / NCCIH NIH HHS / AT / P50 AT002779; United States / NCRR NIH HHS / RR / M01 RR000102; United States / NCI NIH HHS / CA / P01-CA55819; United States / NCI NIH HHS / CA / CA106802; United States / NCI NIH HHS / CA / CA109465; United States / NCI NIH HHS / CA / R01 CA106802; United States / NCCIH NIH HHS / AT / P50-AT02779; United States / NCI NIH HHS / CA / R01 CA109465; United States / NCI NIH HHS / CA / P01 CA055819; United States / NCRR NIH HHS / RR / M01-RR00102
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Biomarkers; 0 / HMGB Proteins; 0 / Immunoglobulin G; 0 / SOX2 protein, human; 0 / SOXB1 Transcription Factors; 0 / Transcription Factors
  • [Other-IDs] NLM/ PMC2118551
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96. Kristinsson SY, Tang M, Pfeiffer RM, Björkholm M, Blimark C, Mellqvist UH, Wahlin A, Turesson I, Landgren O: Monoclonal gammopathy of undetermined significance and risk of skeletal fractures: a population-based study. Blood; 2010 Oct 14;116(15):2651-5
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  • [Title] Monoclonal gammopathy of undetermined significance and risk of skeletal fractures: a population-based study.
  • On the basis of small numbers, patients with monoclonal gammopathy of undetermined significance (MGUS) have been reported to have an increased fracture risk.
  • Using population-based data from Sweden, we assessed the risks of fractures in 5326 MGUS patients diagnosed from 1958 to 2006, compared with 20 161 matched controls.
  • MGUS patients had an increased risk of any fracture at 5 (hazard ratio [HR] = 1.74; 95% confidence interval [CI], 1.58-1.92) and 10 (HR = 1.61; 95% CI, 1.49-1.74) years.
  • The risk was significantly higher for axial (skull, vertebral/pelvis, and sternum/costae) compared with distal (arm and leg) fractures (P < .001).
  • Risks for fractures did not differ by isotype or M protein concentration at diagnosis.
  • MGUS patients with (versus without) fractures had no excess risk of MM or Waldenström macroglobulinemia.
  • Our findings may have implications for the development of better prophylaxis for bone disease in MGUS, and they provide novel clues on pathogenesis of MM bone disease.

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  • (PMID = 20610813.001).
  • [ISSN] 1528-0020
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] ENG
  • [Grant] United States / Intramural NIH HHS / /
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Immunoglobulin Isotypes
  • [Other-IDs] NLM/ PMC3324256
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97. Jain M, Ascensao J, Schechter GP: Familial myeloma and monoclonal gammopathy: a report of eight African American families. Am J Hematol; 2009 Jan;84(1):34-8
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  • [Title] Familial myeloma and monoclonal gammopathy: a report of eight African American families.
  • We report here eight African American families with familial multiple myeloma and monoclonal gammopathy identified over a 30 year period.
  • Six patients with multiple myeloma (MM) and two with monoclonal gammopathy of unknown significance (MGUS) reported a family history of MM or had family members with MGUS found on screening.
  • In the eight families, 21 of 58 first degree relatives had a plasma cell dyscrasia including 12 MM, eight MGUS, and one amyloidosis patient(s).
  • Two MM families each had two additional first degree relatives with MGUS, with three generations involved in one family.
  • Anticipation was suggested in two families with parent-child pairs with monoclonal gammopathy.
  • The eight pedigrees had 66 members, 21 of whom had a diagnosis of cancer, including non-Hodgkin lymphoma and Hodgkin disease, or a clonal myeloproliferative disorder other than MM.
  • Although the mode of genetic transmission and anticipation cannot be confirmed due to the small sample size, the increased number of MM and MGUS family members suggests underlying genetic susceptibility factors for plasma cell dyscrasias and possibly for other cancers in these families.
  • [MeSH-major] African Americans / genetics. Genetic Predisposition to Disease. Multiple Myeloma / genetics. Pedigree
  • [MeSH-minor] Adult. Aged. Female. Hodgkin Disease / genetics. Humans. Lymphoma, Non-Hodgkin / genetics. Male. Middle Aged. Monoclonal Gammopathy of Undetermined Significance / genetics

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  • (PMID = 19037864.001).
  • [ISSN] 1096-8652
  • [Journal-full-title] American journal of hematology
  • [ISO-abbreviation] Am. J. Hematol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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98. Eurelings M, Lokhorst HM, Kalmijn S, Wokke JH, Notermans NC: Malignant transformation in polyneuropathy associated with monoclonal gammopathy. Neurology; 2005 Jun 28;64(12):2079-84

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Malignant transformation in polyneuropathy associated with monoclonal gammopathy.
  • OBJECTIVE: To assess the frequency of hematologic malignancies at diagnosis and to determine the incidence and predictors of malignant transformation during follow-up in patients with polyneuropathy associated with monoclonal gammopathy.
  • RESULTS: Of 193 patients with polyneuropathy associated with monoclonal gammopathy, 17 patients had a hematologic malignancy at diagnosis.
  • The incidence rate of malignant transformation in 176 patients without a malignancy at diagnosis was 2.7/100 patient years.
  • CONCLUSIONS: Since hematologic malignancies occur frequently in polyneuropathy associated with monoclonal gammopathy, the authors suggest that all patients should be screened at diagnosis and subsequently during follow-up if malignant transformation is suspected.
  • [MeSH-major] Cell Transformation, Neoplastic / immunology. Hematologic Neoplasms / epidemiology. Hematologic Neoplasms / immunology. Paraproteinemias / complications. Paraproteinemias / epidemiology. Polyneuropathies / complications. Polyneuropathies / epidemiology
  • [MeSH-minor] Aged. Cohort Studies. Connectin. Disease Progression. Female. Fever / immunology. Fever / physiopathology. Follow-Up Studies. Humans. Incidence. Male. Middle Aged. Muscle Proteins / blood. Muscle Proteins / immunology. Netherlands / epidemiology. Predictive Value of Tests. Weight Loss / immunology

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  • (PMID = 15985576.001).
  • [ISSN] 1526-632X
  • [Journal-full-title] Neurology
  • [ISO-abbreviation] Neurology
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Connectin; 0 / Muscle Proteins
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99. Weiss BM, Kuehl WM: Advances in understanding monoclonal gammopathy of undetermined significance as a precursor of multiple myeloma. Expert Rev Hematol; 2010 Apr;3(2):165-74
ClinicalTrials.gov. clinical trials - ClinicalTrials.gov .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Advances in understanding monoclonal gammopathy of undetermined significance as a precursor of multiple myeloma.
  • Monoclonal gammopathy of undetermined significance (MGUS) affects at least 3% of the population above the age of 50 and is the precursor to multiple myeloma (MM), an incurable malignancy of plasma cells.
  • Recent advances in MGUS include: an improved understanding of the pathogenesis of MGUS and its progression to MM, involving molecular events intrinsic to the malignant plasma cell as well as the microenvironment; novel techniques to assess risk for progression to MM using serum-free light-chain analysis and immunophenotyping; and a renewed interest in chemoprevention of MM.
  • In the future, continued improvement in our understanding of MGUS will lead to the development of better biomarkers for prognosis and therapies for chemoprevention of MM.
  • [MeSH-major] Multiple Myeloma / diagnosis. Paraproteinemias / diagnosis

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  • (PMID = 20473362.001).
  • [ISSN] 1747-4094
  • [Journal-full-title] Expert review of hematology
  • [ISO-abbreviation] Expert Rev Hematol
  • [Language] eng
  • [Databank-accession-numbers] ClinicalTrials.gov/ NCT00480363
  • [Grant] United States / Intramural NIH HHS / / Z99 CA999999; United States / Intramural NIH HHS / / ZIA SC006581-26
  • [Publication-type] Journal Article; Research Support, N.I.H., Intramural; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Immunoglobulin Light Chains; EC 3.6.5.2 / ras Proteins
  • [Other-IDs] NLM/ NIHMS199922; NLM/ PMC2869099
  • [Keywords] NOTNLM ; MGUS / monoclonal gammopathy of undetermined significance / multiple myeloma / pathogenesis
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100. Josselin N, Libouban H, Dib M, Ifrah N, Legrand E, Baslé MF, Audran M, Chappard D: Quantification of dendritic cells and osteoclasts in the bone marrow of patients with monoclonal gammopathy. Pathol Oncol Res; 2009 Mar;15(1):65-72

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Quantification of dendritic cells and osteoclasts in the bone marrow of patients with monoclonal gammopathy.
  • The purpose of this study was to find histological clues for reliable differentiation between monoclonal gammopathy of undetermined significance (MGUS) and myeloma when clinical parameters are controversial.
  • Differential appearance of dendritic cells and osteoclasts, two cell types developing from the monocytic lineage upon distinct cytokine activation profile, might be a useful approach.
  • Patients were classified by the World Health Organization criteria but histopathological criteria were more adapted to identify MGUS (53 cases), myeloma (46), B-cell lymphoma (six) since six myeloma were not correctly classified.
  • The number of marrow dendritic cell was significantly increased with B-cell lymphoma >MGUS >myeloma > controls.
  • Dendritic cell were often mixed with lymphoma cells.
  • B-cell lymphomas had a considerable increase in dendritic cell but presented mononucleated osteoclasts.
  • These findings can help in the classification of MGUS in the early stages of the disease and could help to propose preventive treatments.
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Diagnosis, Differential. Female. Flow Cytometry. Humans. Lymphoma, B-Cell / metabolism. Lymphoma, B-Cell / pathology. Male. Middle Aged. Multiple Myeloma / metabolism. Multiple Myeloma / pathology. Prognosis

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  • (PMID = 18752046.001).
  • [ISSN] 1219-4956
  • [Journal-full-title] Pathology oncology research : POR
  • [ISO-abbreviation] Pathol. Oncol. Res.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Netherlands
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