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1. Chiecchio L, Dagrada GP, Protheroe RK, Stockley DM, Smith AG, Orchard KH, Cross NC, Harrison CJ, Ross FM, UK Myeloma Forum: Loss of 1p and rearrangement of MYC are associated with progression of smouldering myeloma to myeloma: sequential analysis of a single case. Haematologica; 2009 Jul;94(7):1024-8
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Loss of 1p and rearrangement of MYC are associated with progression of smouldering myeloma to myeloma: sequential analysis of a single case.
  • We report serial genetic studies on a young female patient initially diagnosed with asymptomatic smouldering myeloma who progressed to symptomatic myeloma 4.5 years after presentation.
  • An unbalanced translocation, der(14)t(4;14)(p16;q32), was initially found in all plasma cells plus deletions of other chromosomal regions as detected by array-based comparative genomic hybridization.
  • Deletion of chromosome 13 was observed in a minor population of plasma cells (<20%) for the first two years, increasing to 100% of plasma cells by the time of multiple myeloma diagnosis.
  • Loss of 1p and a rearrangement of MYC were first observed in a small population of plasma cells one year prior to the clinical diagnosis of multiple myeloma, but these subclones increased rapidly in size to become the major population suggesting that they were directly involved in the transformation process.
  • This case report provides a unique insight into the mechanisms of disease progression from smouldering multiple myeloma to multiple myeloma.
  • [MeSH-major] Chromosome Aberrations. Chromosome Deletion. Chromosomes, Human, Pair 1 / ultrastructure. Multiple Myeloma / genetics. Proto-Oncogene Proteins c-myc / genetics. Translocation, Genetic

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  • (PMID = 19454499.001).
  • [ISSN] 1592-8721
  • [Journal-full-title] Haematologica
  • [ISO-abbreviation] Haematologica
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Italy
  • [Chemical-registry-number] 0 / Proto-Oncogene Proteins c-myc
  • [Other-IDs] NLM/ PMC2704316
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2. Musto P, Petrucci MT, Bringhen S, Guglielmelli T, Caravita T, Bongarzoni V, Andriani A, D'Arena G, Balleari E, Pietrantuono G, Boccadoro M, Palumbo A, GIMEMA (Italian Group for Adult Hematologic Diseases)/Multiple Myeloma Working Party and the Italian Myeloma Network: A multicenter, randomized clinical trial comparing zoledronic acid versus observation in patients with asymptomatic myeloma. Cancer; 2008 Oct 1;113(7):1588-95
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] A multicenter, randomized clinical trial comparing zoledronic acid versus observation in patients with asymptomatic myeloma.
  • BACKGROUND: Bisphosphonates (BPs) are effective in the prevention and treatment of skeletal-related events (SREs) in patients with symptomatic myeloma who are receiving chemotherapy.
  • Few studies published to date have explored the role of BPs in patients with untreated, asymptomatic myeloma (AM).
  • RESULTS: After a median follow-up of 64.7 person-months, 44.4% of patients in the zoledronic acid group and 45.1% of the control group progressed to 'symptomatic' myeloma requiring chemotherapy (P = .9307).
  • More frequent adverse events observed in the zoledronic acid-treated group were asymptomatic hypocalcemia and fever.
  • [MeSH-major] Bone Density Conservation Agents / therapeutic use. Bone Diseases / prevention & control. Diphosphonates / therapeutic use. Imidazoles / therapeutic use. Multiple Myeloma / drug therapy

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  • [ErratumIn] Cancer. 2008 Nov 15;113(10):2835
  • (PMID = 18683218.001).
  • [ISSN] 0008-543X
  • [Journal-full-title] Cancer
  • [ISO-abbreviation] Cancer
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase III; Comparative Study; Journal Article; Multicenter Study; Randomized Controlled Trial
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Bone Density Conservation Agents; 0 / Diphosphonates; 0 / Imidazoles; 6XC1PAD3KF / zoledronic acid
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3. Nakahara T, Utsugi T, Ohyama Y, Tomono S, Sato K, Takagi H, Murakami H, Hasegawa A, Kurabayashi M: Type 2 diabetes mellitus complicated with smoldering myeloma and non-alcoholic steatohepatitis. Intern Med; 2005 Aug;44(8):838-42
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  • [Title] Type 2 diabetes mellitus complicated with smoldering myeloma and non-alcoholic steatohepatitis.
  • We report a 59-year-old woman with type 2 diabetes mellitus (DM) complicated with smoldering myeloma and non-alcoholic steatohepatitis.
  • A diagnosis of smoldering myeloma was made on the basis of elevation of IgA, M-protein (type:IgA-lambda) and histological findings of bone marrow without bone lesion.
  • To date, there are no reports of cases with DM, NASH and myeloma.
  • [MeSH-major] Diabetes Mellitus, Type 2 / complications. Fatty Liver / complications. Multiple Myeloma / complications


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4. Rosiñol L, Carrió A, Bladé J, Queralt R, Aymerich M, Cibeira MT, Esteve J, Rozman M, Campo E, Montserrat E: Comparative genomic hybridisation identifies two variants of smoldering multiple myeloma. Br J Haematol; 2005 Sep;130(5):729-32
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  • [Title] Comparative genomic hybridisation identifies two variants of smoldering multiple myeloma.
  • Two variants of smoldering multiple myeloma (SMM) have been recognised: (i) an evolving type, characterised by a progressive increase in the M-protein size and short time to progression to overt multiple myeloma (MM) and (ii) a non-evolving type, with a long-lasting, stable M-protein and longer time to progression.
  • [MeSH-major] Chromosomes, Human, Pair 13. Multiple Myeloma / classification. Myeloma Proteins / genetics

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  • (PMID = 16115129.001).
  • [ISSN] 0007-1048
  • [Journal-full-title] British journal of haematology
  • [ISO-abbreviation] Br. J. Haematol.
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Myeloma Proteins; 0 / multiple myeloma M-proteins
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5. 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-major] Multiple Myeloma. Paraproteinemias

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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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6. 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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  • [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).
  • The risk of progression to multiple myeloma (MM) or a related disorder is 1% per year.
  • 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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7. Siniscalchi A, Stasi R, Fratoni S, de Fabritiis P, Caravita T: Management of immune thrombocytopoenia in a patient with newly-diagnosed smouldering myeloma and colorectal cancer. BMJ Case Rep; 2009;2009

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Management of immune thrombocytopoenia in a patient with newly-diagnosed smouldering myeloma and colorectal cancer.
  • Immune thrombocytopoenia (ITP) is one of the most common autoimmune manifestations of B cell lymphoproliferative diseases.
  • The association with multiple myeloma (MM) and solid tumours is rare.
  • Here, a case of ITP associated with asymptomatic multiple myeloma and colon carcinoma, refractory to standard therapy and responsive to rituximab, is described.
  • ITP should be considered in the differential diagnosis of thrombocytopoenia in MM and colon cancer.

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  • (PMID = 21686970.001).
  • [ISSN] 1757-790X
  • [Journal-full-title] BMJ case reports
  • [ISO-abbreviation] BMJ Case Rep
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Other-IDs] NLM/ PMC3028323
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8. Kyle RA, Remstein ED, Therneau TM, Dispenzieri A, Kurtin PJ, Hodnefield JM, Larson DR, Plevak MF, Jelinek DF, Fonseca R, Melton LJ 3rd, Rajkumar SV: Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma. N Engl J Med; 2007 Jun 21;356(25):2582-90
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma.
  • BACKGROUND: Smoldering (asymptomatic) multiple myeloma is an asymptomatic plasma-cell proliferative disorder associated with a high risk of progression to symptomatic multiple myeloma or amyloidosis.
  • METHODS: We searched a computerized database and reviewed the medical records of all patients at Mayo Clinic who fulfilled the criteria of the International Myeloma Working Group for the diagnosis of smoldering multiple myeloma between 1970 and 1995.
  • RESULTS: During the 26-year period, 276 patients fulfilled the criteria for smoldering multiple myeloma.
  • During 2131 cumulative person-years of follow-up, symptomatic multiple myeloma or amyloidosis developed in 163 persons (59%).
  • At diagnosis, significant risk factors for progression included the serum level and type of monoclonal protein, the presence of urinary light chain, the extent and pattern of bone marrow involvement, and the reduction in uninvolved immunoglobulins.
  • The proportion of plasma cells in the bone marrow and the serum monoclonal protein level were combined to create a risk-stratification model with three distinct prognostic groups.
  • CONCLUSIONS: The risk of progression from smoldering multiple myeloma to symptomatic disease is related to the proportion of bone marrow plasma cells and the serum monoclonal protein level at diagnosis.
  • [MeSH-major] Antibodies, Monoclonal / blood. Bone Marrow Cells / immunology. Multiple Myeloma. Plasma Cells


9. 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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  • [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.
  • 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.
  • Information on smoldering multiple myeloma is included.
  • [MeSH-major] Monoclonal Gammopathy of Undetermined Significance / diagnosis. Monoclonal Gammopathy of Undetermined Significance / physiopathology. Multiple Myeloma / physiopathology

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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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10. Rajkumar SV: MGUS and smoldering multiple myeloma: update on pathogenesis, natural history, and management. Hematology Am Soc Hematol Educ Program; 2005;:340-5
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  • [Title] MGUS and smoldering multiple myeloma: update on pathogenesis, natural history, and management.
  • Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic, pre-malignant disorders characterized by monoclonal plasma cell proliferation in the bone marrow and absence of end-organ damage.

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  • (PMID = 16304401.001).
  • [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 / 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 / Glycoproteins; 0 / Immunoglobulin Heavy Chains; 0 / Myeloma Proteins; 0 / multiple myeloma M-proteins; 0 / protein M (glycoprotein)
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11. Boullosa DA, Leicht AS, Tuimil JL: Impact of fire-fighters training on a female with smoldering multiple myeloma. J Sports Med Phys Fitness; 2010 Sep;50(3):326-9
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  • [Title] Impact of fire-fighters training on a female with smoldering multiple myeloma.
  • The purpose of this study was to examine the influence of a fire-fighting training regime on the cardiac autonomic control of a middle-aged female diagnosed with smoldering multiple myeloma (SMM).
  • [MeSH-major] Heart Rate / physiology. Multiple Myeloma / physiopathology. Occupations. Physical Education and Training

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  • (PMID = 20842094.001).
  • [ISSN] 0022-4707
  • [Journal-full-title] The Journal of sports medicine and physical fitness
  • [ISO-abbreviation] J Sports Med Phys Fitness
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Italy
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12. Xiong Y, Donovan KA, Kline MP, Gornet MK, Moon-Tasson LL, Lacy MQ, Dispenzieri A, Gertz MA, Greipp PR, Lust JA: Identification of two groups of smoldering multiple myeloma patients who are either high or low producers of interleukin-1. J Interferon Cytokine Res; 2006 Feb;26(2):83-95
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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 two groups of smoldering multiple myeloma patients who are either high or low producers of interleukin-1.
  • Interleukin-1beta (IL-1beta) is abnormally expressed by the plasma cells obtained from myeloma patients, and it is a potent inducer of the important myeloma growth factor, IL-6.
  • We investigated whether levels of IL-1beta biologic activity might distinguish different groups of patients with smoldering multiple myeloma (SMM).
  • Using this IL-1beta bioassay, we found that it is sensitive at < 1 pg/ml of recombinant IL-1beta and that IL-1beta biologic activity is detectable with either mature or pro-IL-1beta-transduced myeloma cell lines.
  • Patients with active myeloma induced quantitatively higher levels of stromal cell IL-6 production when compared with those with monoclonal gammopathy of undetermined significance (MGUS).
  • [MeSH-major] Interleukin-1beta / biosynthesis. Multiple Myeloma / diagnosis. Multiple Myeloma / metabolism
  • [MeSH-minor] Bone Marrow Cells / metabolism. Bone Marrow Cells / pathology. Cell Line, Tumor. Humans. Interleukin-6 / biosynthesis. Monoclonal Gammopathy of Undetermined Significance / diagnosis. Monoclonal Gammopathy of Undetermined Significance / metabolism. Stromal Cells / metabolism. Stromal Cells / pathology. Syndecans / metabolism. Transduction, Genetic

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  • (PMID = 16487028.001).
  • [ISSN] 1079-9907
  • [Journal-full-title] Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research
  • [ISO-abbreviation] J. Interferon Cytokine Res.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA62242; United States / NCI NIH HHS / CN / CN65125
  • [Publication-type] Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Interleukin-1beta; 0 / Interleukin-6; 0 / Syndecans
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13. 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

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [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.
  • 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.
  • 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.
  • 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.

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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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14. Rajkumar SV, Dispenzieri A, Kyle RA: Monoclonal gammopathy of undetermined significance, Waldenström macroglobulinemia, AL amyloidosis, and related plasma cell disorders: diagnosis and treatment. Mayo Clin Proc; 2006 May;81(5):693-703
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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, Waldenström macroglobulinemia, AL amyloidosis, and related plasma cell disorders: diagnosis and treatment.
  • The spectrum of plasma cell disorders is broad.
  • Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma are asymptomatic disorders characterized by monoclonal plasma cell proliferation in the bone marrow in the absence of end-organ damage.
  • Waldenström macroglobulinemia typically involves an ontogenically less mature lymphoplasmacytic bone marrow cell and is characterized by secretion of a monoclonal IgM protein.
  • Solitary plasmacytoma is the only known potentially curable plasma cell disorder.
  • [MeSH-minor] Humans. Immunoglobulin Light Chains / physiology. Plasmacytoma / diagnosis. Plasmacytoma / therapy. Prognosis

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  • [ErratumIn] Mayo Clin Proc. 2006 Nov;81(11):1509
  • (PMID = 16706268.001).
  • [ISSN] 0025-6196
  • [Journal-full-title] Mayo Clinic proceedings
  • [ISO-abbreviation] Mayo Clin. Proc.
  • [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] United States
  • [Chemical-registry-number] 0 / Immunoglobulin Light Chains
  • [Number-of-references] 107
  •  go-up   go-down


15. Danilatou V, Liapi D, Psyllaki M, Chatzivasili A, Chronaki I, Heliakis P: Neurofibromatosis type I and smoldering multiple myeloma: a case report. Hematology; 2006 Feb;11(1):45-8
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  • [Title] Neurofibromatosis type I and smoldering multiple myeloma: a case report.
  • We present a case of a 64-year-old woman with neurofibromatosis (NF1) and smoldering multiple myeloma (SMM).
  • SMM was diagnosed 9 years ago when the asymptomatic patient was found to have mild anemia, IgA paraproteinemia, hypogammaglobulinemia, osteopenia without any lytic bone lesions and bone marrow plasmacytosis.
  • Forty-two months after diagnosis she had a femoral fracture and since then biphosphonates have been administered intravenously, once monthly.
  • We will discuss the probable pathogenesis of plasma cell dyscrasia in NF1 patients, as well as the likely antimyeloma activity of biphoshonates.
  • [MeSH-major] Bone Density Conservation Agents / administration & dosage. Diphosphonates / administration & dosage. Multiple Myeloma / drug therapy. Multiple Myeloma / etiology. Neurofibromatosis 1 / complications. Neurofibromatosis 1 / drug therapy

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  • (PMID = 16522549.001).
  • [ISSN] 1024-5332
  • [Journal-full-title] Hematology (Amsterdam, Netherlands)
  • [ISO-abbreviation] Hematology
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Bone Density Conservation Agents; 0 / Diphosphonates; 0 / Immunoglobulin A; 0 / Paraproteins
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16. Pérez-Persona E, Vidriales MB, Mateo G, García-Sanz R, Mateos MV, de Coca AG, Galende J, Martín-Nuñez G, Alonso JM, de Las Heras N, Hernández JM, Martín A, López-Berges C, Orfao A, San Miguel JF: New criteria to identify risk of progression in monoclonal gammopathy of uncertain significance and smoldering multiple myeloma based on multiparameter flow cytometry analysis of bone marrow plasma cells. Blood; 2007 Oct 1;110(7):2586-92
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  • [Title] New criteria to identify risk of progression in monoclonal gammopathy of uncertain significance and smoldering multiple myeloma based on multiparameter flow cytometry analysis of bone marrow plasma cells.
  • Monoclonal gammopathy of uncertain significance (MGUS) and smoldering multiple myeloma (SMM) are plasma cell disorders with a risk of progression of approximately 1% and 10% per year, respectively.
  • We have previously shown that the proportion of bone marrow (BM) aberrant plasma cells (aPCs) within the BMPC compartment (aPC/BMPC) as assessed by flow cytometry (FC) contributes to differential diagnosis between MGUS and multiple myloma (MM).
  • Patients with a marked predominance of aPCs/BMPC (> or = 95%) at diagnosis displayed a significantly higher risk of progression both in MGUS and SMM (P< .001).
  • Our results show that multiparameter FC evaluation of BMPC at diagnosis is a valuable tool that could help to individualize the follow-up strategy for MGUS and SMM patients.
  • [MeSH-major] Bone Marrow Cells / pathology. Multiple Myeloma / classification. Multiple Myeloma / pathology. Paraproteinemias / classification. Paraproteinemias / pathology. Plasma Cells / pathology


17. 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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  • [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.
  • It accounts for approximately 10% of all myelomas, and the median time to progression to a symptomatic multiple myeloma ranges from 2 to 3 years.
  • 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").
  • 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.
  • 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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18. 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.
  • 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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19. 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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  • [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.
  • 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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20. Harousseau JL: Optimising patient outcomes in myeloma. Cancer Treat Rev; 2010 May;36 Suppl 2:S33-5
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  • [Title] Optimising patient outcomes in myeloma.
  • Multiple myeloma (MM) is an incurable disease, and the goal of therapy is to prolong survival.
  • With the aim of prolonging survival, trials are currently evaluating newer therapies as long-term maintenance therapy or as prevention therapy for patients with smouldering myeloma.
  • Given that these patients are often asymptomatic and free of clinically active disease, success in this setting depends highly on long-term tolerability of these agents.
  • [MeSH-major] Multiple Myeloma / drug therapy

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  • [Copyright] Copyright 2010 Elsevier Ltd. All rights reserved.
  • (PMID = 20472187.001).
  • [ISSN] 1532-1967
  • [Journal-full-title] Cancer treatment reviews
  • [ISO-abbreviation] Cancer Treat. Rev.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] Netherlands
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Boronic Acids; 0 / Pyrazines; 4Z8R6ORS6L / Thalidomide; 69G8BD63PP / Bortezomib; F0P408N6V4 / lenalidomide
  • [Number-of-references] 18
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21. Barlogie B, van Rhee F, Shaughnessy JD Jr, Epstein J, Yaccoby S, Pineda-Roman M, Hollmig K, Alsayed Y, Hoering A, Szymonifka J, Anaissie E, Petty N, Kumar NS, Srivastava G, Jenkins B, Crowley J, Zeldis JB: Seven-year median time to progression with thalidomide for smoldering myeloma: partial response identifies subset requiring earlier salvage therapy for symptomatic disease. Blood; 2008 Oct 15;112(8):3122-5
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  • [Title] Seven-year median time to progression with thalidomide for smoldering myeloma: partial response identifies subset requiring earlier salvage therapy for symptomatic disease.
  • Smoldering multiple myeloma (SMM) is usually followed expectantly without therapy.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Bone Marrow / pathology. Diphosphonates / administration & dosage. Immunosuppressive Agents / administration & dosage. Multiple Myeloma / drug therapy. Multiple Myeloma / prevention & control. Precancerous Conditions / drug therapy. Thalidomide / administration & dosage

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  • (PMID = 18669874.001).
  • [ISSN] 1528-0020
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Databank-accession-numbers] ClinicalTrials.gov/ NCT00083382
  • [Grant] United States / NCI NIH HHS / CA / P01 CA055819; United States / NCI NIH HHS / CA / CA55819
  • [Publication-type] Clinical Trial, Phase II; Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Diphosphonates; 0 / Immunosuppressive Agents; 4Z8R6ORS6L / Thalidomide; OYY3447OMC / pamidronate
  • [Other-IDs] NLM/ PMC2569167
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22. Jhaveri A, Muggia F: Novel therapies delay the progression of smoldering multiple myeloma: Case report and discussion. Ecancermedicalscience; 2010;4:182
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Novel therapies delay the progression of smoldering multiple myeloma: Case report and discussion.
  • This clinical vignette illustrates how our therapeutic approaches to early stages of multiple myeloma have changed over the past decade with novel therapies reducing disease and preventing disease progression.
  • Recent paradigms of multiple myeloma describe the disease as a spectrum of clinical stages, including asymptomatic 'smoldering' states that progress to symptomatic states.
  • The average 5-year survival rate of patients with multiple myeloma diagnosed between 1996 and 2004 according to surveillance epidemiology and end results (SEER) data is 35.9%.
  • Multiple trials have shown an increased benefit of these newer agents over prior multiple myeloma treatment regimens.
  • At 13 years and 8 months from diagnosis, our patient is doing well, and thus is a model of how long-term control of multiple myeloma prolongs survival.

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  • (PMID = 22276034.001).
  • [ISSN] 1754-6605
  • [Journal-full-title] Ecancermedicalscience
  • [ISO-abbreviation] Ecancermedicalscience
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Other-IDs] NLM/ PMC3234033
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23. Pérez-Persona E, Mateo G, García-Sanz R, Mateos MV, de Las Heras N, de Coca AG, Hernández JM, Galende J, Martín-Nuñez G, Bárez A, Alonso JM, Martín A, López-Berges C, Orfao A, San Miguel JF, Vidriales MB: Risk of progression in smouldering myeloma and monoclonal gammopathies of unknown significance: comparative analysis of the evolution of monoclonal component and multiparameter flow cytometry of bone marrow plasma cells. Br J Haematol; 2010 Jan;148(1):110-4
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  • [Title] Risk of progression in smouldering myeloma and monoclonal gammopathies of unknown significance: comparative analysis of the evolution of monoclonal component and multiparameter flow cytometry of bone marrow plasma cells.
  • The present study explored the impact of two novel criteria; having >95% abnormal plasma cells by flow cytometry at diagnosis and the evolving subtype of the disease, as predictors of progression in 61 smouldering multiple myeloma (SMM) and 311 monoclonal gammopathy of unknown significance (MGUS) patients.
  • [MeSH-major] Monoclonal Gammopathy of Undetermined Significance / immunology. Multiple Myeloma / immunology. Plasma Cells / immunology

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  • (PMID = 19821821.001).
  • [ISSN] 1365-2141
  • [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. Asaoku H: [Biochemical and immunological findings of multiple myeloma]. Nihon Rinsho; 2007 Dec;65(12):2256-60
Hazardous Substances Data Bank. CALCIUM, ELEMENTAL .

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  • [Title] [Biochemical and immunological findings of multiple myeloma].
  • Biochemical and immunological findings of multiple myeloma are reviewed.
  • Rate of abnormal data of biochemical markers in monoclonal gammopathy of undetermined significance (MGUS), asymptomatic myeloma and symptomatic myeloma are reported.
  • Free light chain (FLC) assay is useful for monitoring of intact immunoglobulin myeloma as well as nonsecretory and light chain only myeloma.
  • Phenotypic analysis of plasma cells is useful for differential diagnosis and understanding of proliferative state in multiple myeloma.
  • [MeSH-major] Immunoglobulin Light Chains / blood. Multiple Myeloma / diagnosis
  • [MeSH-minor] Antigens, Surface / analysis. Biomarkers / analysis. Biomarkers / blood. C-Reactive Protein / analysis. Calcium / blood. Creatinine / blood. Diagnosis, Differential. Disease Progression. Humans. L-Lactate Dehydrogenase / blood. Plasma Cells / immunology. Prognosis. Serum Albumin / analysis. beta 2-Microglobulin / blood

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  • (PMID = 18069270.001).
  • [ISSN] 0047-1852
  • [Journal-full-title] Nihon rinsho. Japanese journal of clinical medicine
  • [ISO-abbreviation] Nippon Rinsho
  • [Language] jpn
  • [Publication-type] English Abstract; Journal Article; Review
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Antigens, Surface; 0 / Biomarkers; 0 / Immunoglobulin Light Chains; 0 / Serum Albumin; 0 / beta 2-Microglobulin; 9007-41-4 / C-Reactive Protein; AYI8EX34EU / Creatinine; EC 1.1.1.27 / L-Lactate Dehydrogenase; SY7Q814VUP / Calcium
  • [Number-of-references] 11
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25. Lehtonen J, Kettunen P: Pulmonary hypertension as a dominant clinical picture in a case of amyloidosis and smoldering multiple myeloma. Int J Cardiol; 2007 Jan 31;115(1):e29-30
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  • [Title] Pulmonary hypertension as a dominant clinical picture in a case of amyloidosis and smoldering multiple myeloma.
  • Myocardial biopsy showed amyloidosis and further work-up revealed Salmon-Durie stage 1A multiple myeloma.
  • [MeSH-major] Amyloidosis / complications. Heart Diseases / complications. Hypertension, Pulmonary / etiology. Multiple Myeloma / epidemiology


26. Shimizu K: [Clinical features of multiple myeloma]. Nihon Rinsho; 2007 Dec;65(12):2218-22
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  • [Title] [Clinical features of multiple myeloma].
  • The International Myeloma Working Group (IMWG) has recently proposed a new classification of asymptomatic myeloma and symptomatic myeloma.
  • The distinction between asymptomatic and symptomatic myeloma depends on the presence or absence of the myeloma-related organ or tissue impairment (ROTI) defined by the IMWG.
  • Based on the definition, some patients without clinical symptoms may fall into the "symptomatic" group because of insidious organ impairment by myeloma.
  • Or others with clinical symptoms may fall into "asymptomatic" group, if no organ impairment is proven to be myeloma related.
  • Recognition of the clinical features developed by ROTI is not only important for the diagnosis of symptomatic myeloma but also for the immediate institution of effective treatment.
  • Immediate and proper management of the clinical features of symptomatic myeloma patients will have a great impact on quality of life and survival.
  • [MeSH-major] Multiple Myeloma
  • [MeSH-minor] Amyloidosis / diagnosis. Amyloidosis / etiology. Amyloidosis / therapy. Anemia / diagnosis. Anemia / etiology. Anemia / therapy. Bone Diseases / diagnosis. Bone Diseases / etiology. Bone Diseases / therapy. Humans. Hypercalcemia / diagnosis. Hypercalcemia / etiology. Hypercalcemia / therapy. Kidney Diseases / diagnosis. Kidney Diseases / etiology. Kidney Diseases / therapy. POEMS Syndrome / diagnosis. POEMS Syndrome / etiology. POEMS Syndrome / therapy. Waldenstrom Macroglobulinemia / diagnosis. Waldenstrom Macroglobulinemia / etiology. Waldenstrom Macroglobulinemia / therapy

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  • (PMID = 18069263.001).
  • [ISSN] 0047-1852
  • [Journal-full-title] Nihon rinsho. Japanese journal of clinical medicine
  • [ISO-abbreviation] Nippon Rinsho
  • [Language] jpn
  • [Publication-type] English Abstract; Journal Article; Review
  • [Publication-country] Japan
  • [Number-of-references] 16
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27. Mele A, Offidani M, Visani G, Marconi M, Cambioli F, Nonni M, Catarini M, Brianzoni E, Berbellini A, Ascoli G, Brunori M, Agostini V, Corvatta L, Isidori A, Spinelli A, Gradari M, Leoni P: Technetium-99m sestamibi scintigraphy is sensitive and specific for the staging and the follow-up of patients with multiple myeloma: a multicentre study on 397 scans. Br J Haematol; 2007 Mar;136(5):729-35
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  • [Title] Technetium-99m sestamibi scintigraphy is sensitive and specific for the staging and the follow-up of patients with multiple myeloma: a multicentre study on 397 scans.
  • We evaluated the additional benefit of Technetium(99)-sestamibi (99mTc-MIBI) scanning in comparison with standard X-ray techniques for multiple myeloma patients either at diagnosis or during follow-up.
  • On 229 scans performed at diagnosis, 146 (64%) were positive and 81 cases have discordant X-ray results.
  • As a result of 99mTc-MIBI, 40% of asymptomatic myeloma patients were up-staged.
  • In 22 patients with solitary myeloma, 99mTc-MIBI was positive in 86% of cases and detected more disease sites than X-ray.
  • Among 168 scans performed during follow-up, 99mTc-MIBI presented high specificity in patients showing a complete response (CR; 86%), and correlated with myeloma activity and with response to therapy.
  • We conclude that 99mTc-MIBI scanning is an additional diagnostic tool with a high specificity for the staging and the follow-up of multiple myeloma patients.
  • [MeSH-major] Multiple Myeloma / radionuclide imaging
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Antineoplastic Agents / therapeutic use. Bone Marrow / pathology. C-Reactive Protein / analysis. Female. Follow-Up Studies. Humans. Male. Middle Aged. Neoplasm Invasiveness. Neoplasm Staging. Radiopharmaceuticals. Sensitivity and Specificity. Technetium Tc 99m Sestamibi. Treatment Outcome

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  • (PMID = 17233770.001).
  • [ISSN] 0007-1048
  • [Journal-full-title] British journal of haematology
  • [ISO-abbreviation] Br. J. Haematol.
  • [Language] eng
  • [Publication-type] Evaluation Studies; Journal Article; Multicenter Study
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Radiopharmaceuticals; 9007-41-4 / C-Reactive Protein; 971Z4W1S09 / Technetium Tc 99m Sestamibi
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28. Joshua DE, Brown RD, Ho PJ, Gibson J: Regulatory T cells and multiple myeloma. Clin Lymphoma Myeloma; 2008 Oct;8(5):283-6
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Regulatory T cells and multiple myeloma.
  • Many clinical observations point to active immunologic phenomena in patients with myeloma.
  • These consist of active suppression of the host's immune system and partially successful attempts by the host's immune system to suppress the malignant B-cell population.
  • Clinical conditions such as asymptomatic myeloma, which represents clinical presentation in the plateau phase of the disease, plateau establishment after conventional induction therapy without the ongoing need for therapy, and the positive prognostic importance of the presence of clones of cytotoxic T cells in the peripheral blood of some patients, suggest that host-tumor interaction is an active dynamic state.
  • In myeloma, host-tumor immune interactions are complex.
  • However, patients can clearly exhibit control of their B-cell malignancy for many years with stability of paraprotein levels, demonstrating a homeostasis between tumor and host.
  • In this review, we will discuss the potential importance of Treg cells and their role in myeloma, a disease characterized by a unique set of host-tumor interactions.
  • [MeSH-major] B-Lymphocytes / pathology. Forkhead Transcription Factors / metabolism. Immunologic Factors / metabolism. Multiple Myeloma / immunology. T-Lymphocytes, Regulatory / immunology

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  • (PMID = 18854282.001).
  • [ISSN] 1557-9190
  • [Journal-full-title] Clinical lymphoma & myeloma
  • [ISO-abbreviation] Clin Lymphoma Myeloma
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / FOXP3 protein, human; 0 / Forkhead Transcription Factors; 0 / Immunologic Factors
  • [Number-of-references] 45
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29. Landgren O, Waxman AJ: Multiple myeloma precursor disease. JAMA; 2010 Dec 1;304(21):2397-404
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Multiple myeloma precursor disease.
  • Recent data indicate that multiple myeloma is consistently preceded by the precursor states of monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma.
  • Currently, multiple myeloma is a clinical diagnosis based on manifestations including hypercalcemia, renal failure, anemia, and bone lesions, whereas MGUS and smoldering myeloma are diagnosed based on laboratory abnormalities.
  • (2) elucidating the mechanism of transformation to multiple myeloma; and (3) forming a framework for development of targeted therapies.
  • This case presentation and review discusses the current understanding of myeloma precursor disease and future opportunities for improving personalized management of patients with MGUS or smoldering myeloma, as well as the potential for developing early treatment strategies designed to delay and prevent development of multiple myeloma.

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  • [CommentIn] JAMA. 2011 Mar 16;305(11):1095; author reply 1095 [21406644.001]
  • (PMID = 21119086.001).
  • [ISSN] 1538-3598
  • [Journal-full-title] JAMA
  • [ISO-abbreviation] JAMA
  • [Language] ENG
  • [Grant] United States / Intramural NIH HHS / /
  • [Publication-type] Case Reports; Clinical Conference; Journal Article; Research Support, N.I.H., Intramural
  • [Publication-country] United States
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30. Chiecchio L, Dagrada GP, Ibrahim AH, Dachs Cabanas E, Protheroe RK, Stockley DM, Orchard KH, Cross NC, Harrison CJ, Ross FM, UK Myeloma Forum: Timing of acquisition of deletion 13 in plasma cell dyscrasias is dependent on genetic context. Haematologica; 2009 Dec;94(12):1708-13
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  • [Title] Timing of acquisition of deletion 13 in plasma cell dyscrasias is dependent on genetic context.
  • BACKGROUND: Multiple myeloma, monoclonal gammopathy of undetermined significance and smoldering multiple myeloma harbor common chromosomal abnormalities but the prevalence and relative association of aberrations in these diagnostic groups remains controversial.
  • DESIGN AND METHODS: Chromosome 13 deletion (Delta13), deletion of TP53, ploidy status and immunoglobulin heavy chain (IgH) translocations were evaluated by fluorescence in situ hybridization in patients with monoclonal gammopathy of undetermined significance (n=189), smoldering multiple myeloma (n=127) and multiple myeloma (n=400).
  • RESULTS: Overall, Delta13 (25%, 34% and 47%), 16q23 deletions (6%, 8% and 21%) and 17p13 deletions (3%, 1% and 10%) were less frequent in patients with monoclonal gammopathy of undetermined significance and smoldering multiple myeloma than in those with multiple myeloma.
  • When distinct genetic groups were considered, no differences in the prevalence of Delta13 were found with t(4;14)(p16;q32) and t(14;16)(q32;q23) among the three diagnostic groups; in contrast Delta13 was rarer in t(11;14)(q13;q32) in patients with monoclonal gammopathy (1/28) and smoldering myeloma (2/13) than in those with multiple myeloma (40%).
  • Similar results were seen for the few t(6;14)(p21;q32) cases: 0/3 patients with monoclonal gammopathy or smoldering myeloma had the Delta13, whereas 4/6 (67%) patients with multiple myeloma and this translocation also had the deletion.
  • In multiple myeloma patients with both an IgH translocation and Delta13, the proportions of cells affected by the two abnormalities were similar, as was the case for t(4;14) and t(14;16) monoclonal gammopathy patients positive for Delta13.
  • The observation that Delta13 was extremely rare in monoclonal gammopathy of undetermined significance and smoldering multiple myeloma with translocations directly involving cyclin D genes (CCND1 and CCND3) suggest a possible role of Delta13 in the progression of the disease specifically in these genetic sub-groups. (clinicaltrials.gov identifier: ISRCTN 68454111; UKCRN ID 1176).
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Chromosomes, Human, Pair 11 / genetics. Chromosomes, Human, Pair 14 / genetics. Chromosomes, Human, Pair 16 / genetics. Chromosomes, Human, Pair 17 / genetics. Chromosomes, Human, Pair 4 / genetics. Chromosomes, Human, Pair 6 / genetics. Cyclin D / genetics. Gene Rearrangement. Humans. Immunoglobulin Heavy Chains / genetics. In Situ Hybridization, Fluorescence. Middle Aged. Monoclonal Gammopathy of Undetermined Significance / genetics. Monoclonal Gammopathy of Undetermined Significance / pathology. Multiple Myeloma / genetics. Multiple Myeloma / pathology. Time Factors. Tumor Suppressor Protein p53 / genetics

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  • [Cites] Hematol Oncol Clin North Am. 1999 Dec;13(6):1181-202 [10626144.001]
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  • (PMID = 19996118.001).
  • [ISSN] 1592-8721
  • [Journal-full-title] Haematologica
  • [ISO-abbreviation] Haematologica
  • [Language] eng
  • [Databank-accession-numbers] ISRCTN/ ISRCTN68454111
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Italy
  • [Chemical-registry-number] 0 / Cyclin D; 0 / Immunoglobulin Heavy Chains; 0 / Tumor Suppressor Protein p53
  • [Other-IDs] NLM/ PMC2791926
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31. Gozzetti A, Gennari L, Merlotti D, Salvadori S, De Paola V, Avanzati A, Franci B, Marchini E, Tozzi M, Campagna MS, Nuti R, Lauria F, Martini G: The effects of zoledronic acid on serum lipids in multiple myeloma patients. Calcif Tissue Int; 2008 Apr;82(4):258-62
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] The effects of zoledronic acid on serum lipids in multiple myeloma patients.
  • To explore the effects of ZA on serum lipids, we studied 26 patients with smoldering myeloma at diagnosis.
  • In conclusion, ZA given intravenously at high doses in patients with smoldering myeloma seems to be able to modify the lipid profile with an improvement of atherosclerotic risk index.
  • [MeSH-major] Diphosphonates / pharmacology. Imidazoles / pharmacology. Multiple Myeloma / blood. Multiple Myeloma / drug therapy

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  • (PMID = 18418538.001).
  • [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 / Bone Density Conservation Agents; 0 / Cholesterol, HDL; 0 / Diphosphonates; 0 / Imidazoles; 0 / Lipids; 6XC1PAD3KF / zoledronic acid; 9007-34-5 / Collagen
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32. Adam Z, Bolcák K, Stanícek J, Pour L, Hájek R, Krejcí M, Prásek J, Neubauer J, Mareschova Y, Vorlícek J: [The value of fluorodeoxyglucose positron emission tomography in multiple myeloma]. Vnitr Lek; 2006 Mar;52(3):207-14
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] [The value of fluorodeoxyglucose positron emission tomography in multiple myeloma].
  • The aim of this study was investigate the appearance of multiple myeloma on flurorine--18 fluorodeoxyglucose positron emission tomography (FDG-PET).
  • Furthermore the accuracy of FDG-PET in detecting myeloma lesions and its influence on patient's management were evaluated.
  • METHODS: Altogether 50 patients, 13 patients with newly diagnosed multiple myeloma with negative radiographs, 4 patients with solitary plasmocytoma, 27 patients in remission with suspected relapse and 6 patients with monoclonal gammopathy of unknown significance (MGUS) with suspicion for multiple myeloma or other malignancy underwent FDG-PET examination.
  • RESULTS: Focally increased tracer uptake was observed in 3 (23 %) of newly diagnosed myeloma patients with negative radiographs and was verified with CT or MR with followed indication for therapy.
  • The FDG-PET was negative in two cases of newly diagnosed multiple myeloma with negative radiographs, no focal infiltration on MR imagination, but with anemia, high monoclonal imunoglobulin and bone marrow infiltration, which was indication for therapy.
  • In all other cases FDG-PET negativity in asymptomatic myeloma had good prognostic significance; these patients are without progression after with a median follow up 14 (7-20) months.
  • In 4 cases of them it was due to multiple myeloma relapse, in one case due to ovarial carcinoma.
  • CONCLUSION: In conclusion, FDG PET might contribute to initial staging of radiographs negative multiple myeloma and might be useful for follow up of patients in remission, especially in consecratory multiple myeloma, or in patients with large plasmocelular tumor (> 5 cm) after concomitant radiochemotherapy.
  • [MeSH-major] Fluorodeoxyglucose F18. Multiple Myeloma / radionuclide imaging. Positron-Emission Tomography. Radiopharmaceuticals

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  • [CommentIn] Vnitr Lek. 2006 Mar;52(3):203-4 [16722149.001]
  • (PMID = 16722151.001).
  • [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 / Radiopharmaceuticals; 0Z5B2CJX4D / Fluorodeoxyglucose F18
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33. Martini G, Gozzetti A, Gennari L, Avanzati A, Nuti R, Lauria F: The effect of zoledronic acid on serum osteoprotegerin in early stage multiple myeloma. Haematologica; 2006 Dec;91(12):1720-1
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] The effect of zoledronic acid on serum osteoprotegerin in early stage multiple myeloma.
  • We evaluated the effect of zoledronic acid (ZA) on serum levels of osteoprotegerin (OPG) and the ligand for receptor activator of nuclear factor kappaB (RANKL) in patients with smoldering myeloma.
  • [MeSH-major] Diphosphonates / therapeutic use. Imidazoles / therapeutic use. Multiple Myeloma / blood. Osteoprotegerin / blood

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  • (PMID = 17145616.001).
  • [ISSN] 1592-8721
  • [Journal-full-title] Haematologica
  • [ISO-abbreviation] Haematologica
  • [Language] eng
  • [Publication-type] Comparative Study; Letter
  • [Publication-country] Italy
  • [Chemical-registry-number] 0 / Diphosphonates; 0 / Imidazoles; 0 / Osteoprotegerin; 6XC1PAD3KF / zoledronic acid
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34. Pratt G: The evolving use of serum free light chain assays in haematology. Br J Haematol; 2008 May;141(4):413-22
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  • The new FLC assay has enabled the detection of monoclonal protein in some patients with non-secretory myeloma and amyloidosis that were previously undetectable.
  • FLC measurements are quantitative, correlating with disease activity, and are an advance in monitoring light chain only multiple myeloma, AL amyloidosis, non-secretory and oligo-secretory multiple myeloma.
  • Serum FLC concentrations also reflect the disease course in the majority of myeloma patients producing intact monoclonal immunoglobulin proteins and have been incorporated into the new response criteria.
  • An abnormal FLC ratio has been shown to be a risk factor for progression of monoclonal gammopathy of undetermined significance, smouldering myeloma and solitary plasmacytoma of bone and is prognostic in multiple myeloma.
  • [MeSH-major] Biomarkers, Tumor / blood. Immunoglobulin Light Chains / blood. Multiple Myeloma / diagnosis
  • [MeSH-minor] Hematologic Neoplasms / diagnosis. Humans. Paraproteinemias / diagnosis. Prognosis

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  • [CommentIn] Br J Haematol. 2008 Oct;143(1):143-5; author reply 145-6 [18671704.001]
  • (PMID = 18318757.001).
  • [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
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / Immunoglobulin Light Chains
  • [Number-of-references] 72
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35. Zeldis JB, Knight RD, Jacques C, Tozer A, Bizzari JP: Lenalidomide in multiple myeloma: current role and future directions. Expert Opin Pharmacother; 2010 Apr;11(5):829-42
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  • [Title] Lenalidomide in multiple myeloma: current role and future directions.
  • IMPORTANCE OF THE FIELD: Lenalidomide and other new agents are improving survival of multiple myeloma patients.
  • This review describes current data on lenalidomide in myeloma and how the unique properties of lenalidomide may lend its use in new settings, such as maintenance and preventive therapy.
  • AREAS COVERED IN THIS REVIEW: This review covers the activity of lenalidomide in multiple myeloma, efficacy in both newly diagnosed and relapsed/refractory patients, how to manage effectively common adverse events observed with lenalidomide, and its potential use in new settings based on clinical trials published up to 2009.
  • WHAT THE READER WILL GAIN: This review describes the mechanism of action of lenalidomide in myeloma which provides the basis for its clinical use in newly diagnosed, relapsed/refractory, and high-risk smoldering myeloma in combination with other agents.
  • TAKE HOME MESSAGE: Lenalidomide is an oral immunomodulatory drug that is highly effective in treating multiple myeloma, has a favorable safety profile and is now being evaluated as maintenance therapy, preventive therapy and in combination with other new agents.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Multiple Myeloma / drug therapy
  • [MeSH-minor] Clinical Trials as Topic. Dexamethasone / administration & dosage. Humans. Neoplasm Recurrence, Local. Survival Rate. Thalidomide / administration & dosage. Thalidomide / analogs & derivatives

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  • [ErratumIn] Expert Opin Pharmacother. 2010 Sep;11(13):2273
  • [ErratumIn] Expert Opin Pharmacother. 2011 Mar;12(4):679
  • (PMID = 20210686.001).
  • [ISSN] 1744-7666
  • [Journal-full-title] Expert opinion on pharmacotherapy
  • [ISO-abbreviation] Expert Opin Pharmacother
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Chemical-registry-number] 4Z8R6ORS6L / Thalidomide; 7S5I7G3JQL / Dexamethasone; F0P408N6V4 / lenalidomide
  • [Number-of-references] 87
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36. Kimlinger T, Kline M, Kumar S, Lust J, Witzig T, Rajkumar SV: Differential expression of vascular endothelial growth factors and their receptors in multiple myeloma. Haematologica; 2006 Aug;91(8):1033-40
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  • [Title] Differential expression of vascular endothelial growth factors and their receptors in multiple myeloma.
  • BACKGROUND AND OBJECTIVES: Bone marrow angiogenesis is increased in patients with multiple myeloma (MM) and correlates with disease stage.
  • DESIGN AND METHODS: Previous studies of quantifying vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFR) in plasma cells from patients at different stages of MM found no significant difference in expression between overt MM and earlier pre-malignant stages of the disease namely, monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM).
  • RESULTS: In this report we used quantitative flow cytometry to study cytoplasmic VEGF (cyVEGF) expression (measured as antibody binding capacity) in plasma cells from patients with MM (n = 22), MGUS/SMM (n = 12), and AL-amyloidosis (AL) (n = 9).
  • Using an indirect VEGFR assay that measures VEGF binding, we found VEGF receptors on plasma cells from all groups of patients, with the lowest expression on plasma cells from normal individuals.
  • We detected VEGF R1, VEGF R2, and VEGF R3 on plasma cells from all groups of patients and found receptor expression predominantly in the subset of CD45-positive plasma cells.
  • INTERPRETATION AND CONCLUSIONS: This study supports the concept that VEGF is involved in the pathogenesis of MM, and suggests that VEGF may differentially affect a subset of plasma cells.
  • [MeSH-major] Gene Expression Regulation, Neoplastic. Multiple Myeloma / metabolism. Receptors, Vascular Endothelial Growth Factor / metabolism. Vascular Endothelial Growth Factor A / metabolism
  • [MeSH-minor] Bone Marrow Cells / pathology. Bone Marrow Cells / physiology. Humans. Plasma Cells / metabolism. Plasma Cells / pathology. Reference Values

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  • (PMID = 16870555.001).
  • [ISSN] 1592-8721
  • [Journal-full-title] Haematologica
  • [ISO-abbreviation] Haematologica
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA100080; United States / NCI NIH HHS / CA / CA62242; United States / NCI NIH HHS / CA / CA93842
  • [Publication-type] Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] Italy
  • [Chemical-registry-number] 0 / Vascular Endothelial Growth Factor A; EC 2.7.10.1 / Receptors, Vascular Endothelial Growth Factor
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37. Detweiler-Short K, Hayman S, Gertz MA, Lacy MQ, Dispenzieri A, Kumar S, Zeldenrust SR, Russell SJ, Lust JA, Kyle RA, Greipp PR, Witzig TE, Vincent Rajkumar S: Long-term results of single-agent thalidomide as initial therapy for asymptomatic (smoldering or indolent) myeloma. Am J Hematol; 2010 Oct;85(10):737-40
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  • [Title] Long-term results of single-agent thalidomide as initial therapy for asymptomatic (smoldering or indolent) myeloma.
  • We report the long-term follow-up results of a phase II trial of thalidomide for early-stage multiple myeloma (MM).
  • Patients were eligible if they had smoldering multiple myeloma (SMM) or indolent MM without the need for immediate therapy.
  • Thirty-one patients were enrolled; 29 (19 SMM and 10 indolent MM) were eligible.
  • The median time to progression (TTP) to symptomatic myeloma was 35 months.
  • Median overall survival from diagnosis was 86 months; median survival from onset of symptomatic myeloma was 49 months.

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  • [Copyright] © 2010 Wiley-Liss, Inc.
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  • (PMID = 20730790.001).
  • [ISSN] 1096-8652
  • [Journal-full-title] American journal of hematology
  • [ISO-abbreviation] Am. J. Hematol.
  • [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
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  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 4Z8R6ORS6L / Thalidomide
  • [Other-IDs] NLM/ NIHMS228591; NLM/ PMC3022372
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38. Koski AM, Sikiö A, Forslund T: Teriparatide treatment complicated by malignant myeloma. BMJ Case Rep; 2010;2010
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  • [Title] Teriparatide treatment complicated by malignant myeloma.
  • In malignant myeloma there is an imbalance between osteoclast and osteoblast activity with involvement of the RANKL/OPG system among others.
  • We report a case with monoclonal gammopathy of uncertain significance (MGUS) who developed malignant myeloma after teriparatide treatment and we suggest that in addition to malignant myeloma and smouldering myeloma, MGUS should also be considered contraindicated for teriparatide treatment.
  • [MeSH-major] Fractures, Spontaneous / etiology. Fractures, Spontaneous / radiography. Multiple Myeloma / chemically induced. Osteoporosis, Postmenopausal / drug therapy. Teriparatide / adverse effects

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  • (PMID = 22767690.001).
  • [ISSN] 1757-790X
  • [Journal-full-title] BMJ case reports
  • [ISO-abbreviation] BMJ Case Rep
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 10T9CSU89I / Teriparatide
  • [Other-IDs] NLM/ PMC3027506
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39. Hoffman-Snyder C, Smith BE: Neuromuscular disorders associated with paraproteinemia. Phys Med Rehabil Clin N Am; 2008 Feb;19(1):61-79, vi
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  • This discovery should prompt further evaluation for underlying plasma cell dyscrasias.
  • The most frequent monoclonal disorders associated with neuropathy are smoldering myeloma, multiple myeloma, Waldenström macroglobulinemia, solitary plasmacytoma, systemic immunoglobulin light chain (AL) amyloidosis, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes), and cryoglobulinemia.
  • [MeSH-minor] Female. Humans. Male. Multiple Myeloma / classification. Multiple Myeloma / physiopathology. Risk Factors

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  • (PMID = 18194750.001).
  • [ISSN] 1047-9651
  • [Journal-full-title] Physical medicine and rehabilitation clinics of North America
  • [ISO-abbreviation] Phys Med Rehabil Clin N Am
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Number-of-references] 40
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40. Weiss BM, Abadie J, Verma P, Howard RS, Kuehl WM: A monoclonal gammopathy precedes multiple myeloma in most patients. Blood; 2009 May 28;113(22):5418-22
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] A monoclonal gammopathy precedes multiple myeloma in most patients.
  • Preexisting plasma cell disorders, monoclonal gammopathy of undetermined significance, or smoldering myeloma are present in at least one-third of multiple myeloma patients.
  • However, the proportion of patients with a preexisting plasma cell disorder has never been determined by laboratory testing on prediagnostic sera.
  • We cross-referenced our autologous stem cell transplantation database with the Department of Defense Serum Repository.
  • Serum protein electrophoresis, immunofixation electrophoresis, and serum free light-chain analysis were performed on all sera collected 2 or more years before diagnosis to detect a monoclonal gammopathy (M-Ig).
  • In 30 of 90 patients, 110 prediagnostic samples were available from 2.2 to 15.3 years before diagnosis.
  • Four patients had only one positive sample within 4 years before diagnosis, with all preceding sera negative.
  • All 4 patients with light-chain/nonsecretory myeloma evolved from a light-chain M-Ig.
  • A preexisting M-Ig is present in most multiple myeloma patients before diagnosis.
  • [MeSH-major] Multiple Myeloma / etiology. Paraproteinemias / complications. Precancerous Conditions / complications. Precancerous Conditions / diagnosis


41. Mulligan ME, Badros AZ: PET/CT and MR imaging in myeloma. Skeletal Radiol; 2007 Jan;36(1):5-16
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] PET/CT and MR imaging in myeloma.
  • Myeloma is the most common primary bone malignancy.
  • In the United States, there are an estimated 16,000 new cases and over 11,000 deaths yearly due to myeloma.
  • Plasma cell dyscrasias manifest themselves in a variety of forms that range from MGUS (monoclonal gammopathy of undetermined significance) and smoldering myeloma that require no therapy, to the "malignant" form of multiple myeloma.
  • The role of imaging in the management of myeloma includes: an assessment of the extent of intramedullary bone disease, detection of any extramedullary foci, and severity of the disease at presentation; the identification and characterization of complications; subsequent assessment of disease status.
  • This review will focus on the use of PET/CT and MR imaging for myeloma patients at the time of initial diagnosis and for follow-up management, based on current reports in the literature and our practice at the Marlene and Stewart Greenebaum Cancer Center, University of Maryland Medical Center in Baltimore, USA.
  • [MeSH-major] Bone Neoplasms / diagnosis. Magnetic Resonance Imaging. Multiple Myeloma / diagnosis. Positron-Emission Tomography. Tomography, X-Ray Computed
  • [MeSH-minor] Humans. Neoplasm Staging. Reproducibility of Results

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  • (PMID = 16915386.001).
  • [ISSN] 0364-2348
  • [Journal-full-title] Skeletal radiology
  • [ISO-abbreviation] Skeletal Radiol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] Germany
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42. Ross FM, Chiecchio L, Dagrada G, Protheroe RK, Stockley DM, Harrison CJ, Cross NC, Szubert AJ, Drayson MT, Morgan GJ, UK Myeloma Forum: The t(14;20) is a poor prognostic factor in myeloma but is associated with long-term stable disease in monoclonal gammopathies of undetermined significance. Haematologica; 2010 Jul;95(7):1221-5
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] The t(14;20) is a poor prognostic factor in myeloma but is associated with long-term stable disease in monoclonal gammopathies of undetermined significance.
  • A large series of plasma cell dyscrasias (n=2207) was examined for translocations which deregulate the MAF genes, t(14;20)(q32;q12) and t(14;16)(q32;q23), and their disease behavior was compared to a group characterized by the t(4;14)(p16;q32) where CCND2 is also up-regulated.
  • The t(14;20) showed low prevalence in myeloma (27/1830, 1.5%) and smoldering myeloma (1/148, <1%) with a higher incidence in MGUS (9/193, 5% P=0.005).
  • All three translocations were associated with poor outcome in myeloma, but strikingly all t(14;20) MGUS/smoldering myeloma cases (n=10) had stable, low level disease.
  • In contrast, the 10 t(14;16) and 25 t(4;14) MGUS/smoldering myeloma cases were associated with both evolving and non-evolving disease.
  • None of the associated genetic abnormalities helped to predict for progression from MGUS or smoldering myeloma.
  • [MeSH-major] Monoclonal Gammopathy of Undetermined Significance / genetics. Multiple Myeloma / genetics. Translocation, Genetic

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  • (PMID = 20410185.001).
  • [ISSN] 1592-8721
  • [Journal-full-title] Haematologica
  • [ISO-abbreviation] Haematologica
  • [Language] eng
  • [Grant] United Kingdom / Medical Research Council / / G0100132
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Italy
  • [Other-IDs] NLM/ PMC2895050
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43. Sharma A, Kaushal M, Chaturvedi NK, Yadav R: Cytodiagnosis of multiple myeloma presenting as orbital involvement: a case report. Cytojournal; 2006;3:19

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Cytodiagnosis of multiple myeloma presenting as orbital involvement: a case report.
  • BACKGROUND: Plasma cell neoplasms represent autonomous proliferations of plasma cells and can manifest as diffuse myeloma with systemic involvement (plasma cell myeloma or multiple myeloma), monoclonal gammopathy of undetermined significance (MGUS), or as variants of plasma cell myeloma such as indolent myeloma, smoldering myeloma, osteosclerotic myeloma, plasma cell leukaemia and non-secretory myeloma.
  • Localized neoplastic proliferation of plasma cells presents as solitary plasmacytoma of bone or extramedullary plasmacytoma.
  • Involvement of orbit can occur as a solitary plasmacytoma, or as part of systemic involvement in multiple myeloma, the clinical outcome being significantly worse in the latter setting.
  • Orbital involvement in multiple myeloma is very rare with less than 50 cases reported in the literature.
  • Early cytological diagnosis of such lesions is vital for timely institution of appropriate therapy.
  • As far as we are aware only six previous cases of cytological diagnosis of multiple myeloma involving the orbit are on record.
  • A final diagnosis of multiple myeloma with orbital involvement at presentation was made.
  • CONCLUSION: Present case describes the extremely rare presentation of multiple myeloma with orbital involvement and highlights the utility of cytology in such lesions.
  • Fine needle aspiration diagnosis of plasmacytoma at extramedullary sites offers an opportunity for non-invasive verification of systemic involvement, and thus plays a major role in early diagnosis and management of these patients.

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  • (PMID = 16901345.001).
  • [ISSN] 1742-6413
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  • [ISO-abbreviation] Cytojournal
  • [Language] eng
  • [Publication-type] Journal Article
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  • [Other-IDs] NLM/ PMC1564147
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44. Dispenzieri A, Kyle RA, Katzmann JA, Therneau TM, Larson D, Benson J, Clark RJ, Melton LJ 3rd, Gertz MA, Kumar SK, Fonseca R, Jelinek DF, Rajkumar SV: Immunoglobulin free light chain ratio is an independent risk factor for progression of smoldering (asymptomatic) multiple myeloma. Blood; 2008 Jan 15;111(2):785-9
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Immunoglobulin free light chain ratio is an independent risk factor for progression of smoldering (asymptomatic) multiple myeloma.
  • We hypothesized that increased monoclonal free kappa or lambda immunoglobulin light chains in smoldering multiple myeloma (SMM), as detected by the serum free light chain (FLC) assay, indicates an increased risk of progression to active myeloma.
  • Baseline serum samples obtained within 30 days of diagnosis were available in 273 patients with SMM seen from 1970 to 1995.
  • The extent of abnormality of FLC ratio was independent of SMM risk categories defined by number of bone marrow plasma cells (BMPCs) and size of serum M proteins (BMPC>or=10% and serum M protein>or=3 g/dL; BMPC>or=10% but serum M protein<3 g/dL; and serum M protein>or=3 g/dL but BMPC<10%).


45. Chng WJ, Van Wier SA, Ahmann GJ, Winkler JM, Jalal SM, Bergsagel PL, Chesi M, Trendle MC, Oken MM, Blood E, Henderson K, Santana-Dávila R, Kyle RA, Gertz MA, Lacy MQ, Dispenzieri A, Greipp PR, Fonseca R: A validated FISH trisomy index demonstrates the hyperdiploid and nonhyperdiploid dichotomy in MGUS. Blood; 2005 Sep 15;106(6):2156-61
The Lens. Cited by Patents in .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • Two major genetic categories of multiple myeloma (MM) exist.
  • This is especially true in MGUS where the number of clonal plasma cells is small.
  • Using the criteria of 2 or more trisomies from a 3-chromosome combination, hyperdiploid myeloma can be detected with high specificity.
  • Applying this index on 28 patients with smoldering multiple myeloma (SMM) or MGUS (11 SMM, 17 MGUS) who had normal karyotype, 11 cases of hyperdiploid SMM/MGUS were detected.

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  • (PMID = 15920009.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / CA21 115-25C; United States / NCI NIH HHS / CA / P01 CA62 242; United States / NCI NIH HHS / CA / P50 CA100 707-01; United States / NCI NIH HHS / CA / R01 CA83 724 01
  • [Publication-type] Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Validation Studies
  • [Publication-country] United States
  • [Other-IDs] NLM/ PMC1895145
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46. Sze DM: Clonality detection of expanded T-cell populations in patients with multiple myeloma. Methods Mol Med; 2005;113:257-67
MedlinePlus Health Information. consumer health - Multiple Myeloma.

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Clonality detection of expanded T-cell populations in patients with multiple myeloma.
  • Expanded T-cell clones in the peripheral blood of patients with multiple myeloma and smoldering myeloma are usually CD8 positive and persist over long periods, suggesting that they are the result of chronic antigenic stimulation.
  • The presence of enlarged T-cell clones can be demonstrated as bands other than the germ-line bands on Southern blots probed for the T-cell receptor beta gene (Vbeta), or defined by anti-TCRVbeta monoclonal antibody staining.
  • Furthermore, my colleagues and I have previously shown that the CD57+ T-cells expressing the "expanded" TCRVbeta are monoclonal or biclonal, whereas the CD57- cells are usually polyclonal.
  • [MeSH-major] Multiple Myeloma / immunology. T-Lymphocytes / classification. T-Lymphocytes / immunology
  • [MeSH-minor] Antigens, CD / blood. Base Sequence. Blotting, Southern / methods. CD8-Positive T-Lymphocytes / immunology. CD8-Positive T-Lymphocytes / pathology. Clone Cells. Complementarity Determining Regions / genetics. Complementarity Determining Regions / immunology. DNA Primers. DNA, Complementary / genetics. Flow Cytometry / methods. Humans. Polymerase Chain Reaction / methods. Receptors, Antigen, T-Cell, alpha-beta / genetics. Receptors, Antigen, T-Cell, alpha-beta / immunology

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  • (PMID = 15968109.001).
  • [ISSN] 1543-1894
  • [Journal-full-title] Methods in molecular medicine
  • [ISO-abbreviation] Methods Mol. Med.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antigens, CD; 0 / Complementarity Determining Regions; 0 / DNA Primers; 0 / DNA, Complementary; 0 / Receptors, Antigen, T-Cell, alpha-beta
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47. Nau KC, Lewis WD: Multiple myeloma: diagnosis and treatment. Am Fam Physician; 2008 Oct 1;78(7):853-9
MedlinePlus Health Information. consumer health - Multiple Myeloma.

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Multiple myeloma: diagnosis and treatment.
  • Multiple myeloma, the most common bone malignancy, is occurring with increasing frequency in older persons.
  • Skeletal radiographs are important in staging multiple myeloma and revealing lytic lesions, vertebral compression fractures, and osteoporosis.
  • Magnetic resonance imaging and positron emission tomography or computed tomography are emerging as useful tools in the evaluation of patients with myeloma; magnetic resonance imaging is preferred for evaluating acute spinal compression.
  • Nuclear bone scans and dual energy x-ray absorptiometry have no role in the diagnosis and staging of myeloma.
  • The differential diagnosis of monoclonal gammopathies includes monoclonal gammopathy of uncertain significance, smoldering (asymptomatic) and symptomatic multiple myeloma, amyloidosis, B-cell non-Hodgkin lymphoma, Waldenström macroglobulinemia, and rare plasma cell leukemia and heavy chain diseases.
  • Patients with monoclonal gammopathy of uncertain significance or smoldering multiple myeloma should be followed closely, but not treated.
  • Symptomatic multiple myeloma is treated with chemotherapy followed by autologous stem cell transplantation, if possible.
  • It is important that family physicians recognize and appropriately treat multiple myeloma complications.
  • [MeSH-major] Multiple Myeloma / diagnosis. Multiple Myeloma / therapy
  • [MeSH-minor] Age Factors. Humans. Myeloma Proteins / physiology. Pain / etiology. Plasma Cells / physiology. Risk Factors

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  • (PMID = 18841734.001).
  • [ISSN] 0002-838X
  • [Journal-full-title] American family physician
  • [ISO-abbreviation] Am Fam Physician
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Myeloma Proteins; 0 / multiple myeloma M-proteins
  • [Number-of-references] 29
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48. Salhia B, Baker A, Ahmann G, Auclair D, Fonseca R, Carpten J: DNA methylation analysis determines the high frequency of genic hypomethylation and low frequency of hypermethylation events in plasma cell tumors. Cancer Res; 2010 Sep 1;70(17):6934-44
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] DNA methylation analysis determines the high frequency of genic hypomethylation and low frequency of hypermethylation events in plasma cell tumors.
  • Multiple myeloma (MM) is a plasma cell malignancy of the bone marrow, which evolves from a premalignant stage called monoclonal gammopathy of undetermined significance (MGUS).
  • In some patients, an intermediate stage referred to as smoldering multiple myeloma (SMM) is clinically recognized, with the full-bore malignancy termed MM.
  • We conducted a study to assess differential CpG methylation at 1,500 genic loci during MM progression and profiled CD138(+) plasma cells from MGUS, SMM, and MM specimens; human myeloma cell lines; and normal plasma cell (NPC) samples.
  • Determining the set of critical genes and pathways based on the myeloma methylome is expected to lead to an improved understanding of biological mechanisms involved in myelomagenesis.
  • [MeSH-major] DNA Methylation. Monoclonal Gammopathy of Undetermined Significance / genetics. Multiple Myeloma / genetics

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  • [CommentIn] Epigenomics. 2011 Apr;3(2):143-4 [22232794.001]
  • (PMID = 20736376.001).
  • [ISSN] 1538-7445
  • [Journal-full-title] Cancer research
  • [ISO-abbreviation] Cancer Res.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
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49. Chappard D, Libouban H, Legrand E, Ifrah N, Masson C, Baslé MF, Audran M: Computed microtomography of bone specimens for rapid analysis of bone changes associated with malignancy. Anat Rec (Hoboken); 2010 Jul;293(7):1125-33
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • B-cell malignancies (lymphoma, myeloma) are also associated with marked osteolysis.
  • Histopathological examination of bone biopsies was used for the diagnosis of malignancies and, prior to embedding, microcomputed tomography (microCT) was done on the bone specimens.
  • Patients (247) who presented either a bone metastasis, an overt myeloma, a lymphoma or a monoclonal gammopathy of undetermined significance were studied.
  • MicroCT failed to identify some patients with smoldering myeloma or some lymphomas with microresorption.
  • MicroCT data are obtained within 4 hr and suggest the malignant invasion of bone marrow when excess of bone resorption/formation is obtained.

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  • (PMID = 20583257.001).
  • [ISSN] 1932-8494
  • [Journal-full-title] Anatomical record (Hoboken, N.J. : 2007)
  • [ISO-abbreviation] Anat Rec (Hoboken)
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
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50. Bridoux F, Sirac C, Hugue V, Decourt C, Thierry A, Quellard N, Abou-Ayache R, Goujon JM, Cogné M, Touchard G: Fanconi's syndrome induced by a monoclonal Vkappa3 light chain in Waldenstrom's macroglobulinemia. Am J Kidney Dis; 2005 Apr;45(4):749-57

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • Fanconi's syndrome (FS) is a disorder of sodium-dependent proximal tubule reabsorption, which may complicate plasma cell disorders producing a free monoclonal light chain (LC).
  • FS often occurs in the setting of smoldering myeloma and features cytoplasmic crystalline inclusions of monoclonal kappa LC in proximal tubular cells and malignant plasma cells.
  • Mechanisms other than resistance of LCs to endosomal proteolysis probably are involved in the pathogenesis of FS-associated plasma cell dyscrasias.

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  • (PMID = 15806478.001).
  • [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
  • [Publication-type] Case Reports; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Immunoglobulin M; 0 / Immunoglobulin Variable Region; 0 / Immunoglobulin kappa-Chains; EC 3.4.21.4 / Trypsin
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51. Gabay C, Lamacchia C, Palmer G: IL-1 pathways in inflammation and human diseases. Nat Rev Rheumatol; 2010 Apr;6(4):232-41
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  • Finally, preliminary results indicating that IL-1 targeting is efficacious in type 2 diabetes and smoldering myeloma have further broadened the spectrum of IL-1-driven diseases.

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  • (PMID = 20177398.001).
  • [ISSN] 1759-4804
  • [Journal-full-title] Nature reviews. Rheumatology
  • [ISO-abbreviation] Nat Rev Rheumatol
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Inflammation Mediators; 0 / Interleukin 1 Receptor Antagonist Protein; 0 / Interleukin-1; 0 / Interleukin-1beta; 0 / Receptors, Interleukin
  • [Number-of-references] 119
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52. Brenne AT, Fagerli UM, Shaughnessy JD Jr, Våtsveen TK, Rø TB, Hella H, Zhan F, Barlogie B, Sundan A, Børset M, Waage A: High expression of BCL3 in human myeloma cells is associated with increased proliferation and inferior prognosis. Eur J Haematol; 2009 May;82(5):354-63
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] High expression of BCL3 in human myeloma cells is associated with increased proliferation and inferior prognosis.
  • We experienced that this putative oncogene was a common target gene for growth-promoting cytokines in myeloma cell lines.
  • METHODS: Gene expression of BCL3 was studied in 351 newly diagnosed myeloma patients, 12 patients with smouldering myeloma, 44 patients with monoclonal gammopathy of undetermined significance and 22 healthy individuals.
  • A total of eight different myeloma cell lines were studied.
  • RESULTS: Bcl-3 was induced in myeloma cell lines by interleukin (IL)-6, IL-21, IL-15, tumor necrosis factor-alpha and IGF-1, and its upregulation was associated with increased proliferation of the cells.
  • When this patient population was divided into subgroups based on molecular classification, BCL3 was significantly increased in a poor risk subgroup characterized by overexpression of cell cycle and proliferation related genes.
  • Intracellular localization of Bcl-3 was dependent on type of stimulus given to the cell.
  • CONCLUSION: BCL3 is a common target gene for several growth-promoting cytokines in myeloma cells and high expression of BCL3 at the time of diagnosis is associated with poor prognosis of patients with multiple myeloma (MM).

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  • (PMID = 19191868.001).
  • [ISSN] 1600-0609
  • [Journal-full-title] European journal of haematology
  • [ISO-abbreviation] Eur. J. Haematol.
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / P01 CA055819; United States / NCI NIH HHS / CA / R33 CA097513
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Cytokines; 0 / Proto-Oncogene Proteins; 0 / RNA, Messenger; 0 / Transcription Factors; 0 / proto-oncogene protein bcl-3
  • [Other-IDs] NLM/ PMC2704939
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53. Leone PE, Walker BA, Jenner MW, Chiecchio L, Dagrada G, Protheroe RK, Johnson DC, Dickens NJ, Brito JL, Else M, Gonzalez D, Ross FM, Chen-Kiang S, Davies FE, Morgan GJ: Deletions of CDKN2C in multiple myeloma: biological and clinical implications. Clin Cancer Res; 2008 Oct 01;14(19):6033-41
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Deletions of CDKN2C in multiple myeloma: biological and clinical implications.
  • PURPOSE: Deletions of chromosome 1 have been described in 7% to 40% of cases of myeloma with inconsistent clinical consequences.
  • CDKN2C at 1p32.3 has been identified in myeloma cell lines as the potential target of the deletion.
  • EXPERIMENTAL DESIGN: We analyzed 515 cases of monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and newly diagnosed multiple myeloma using fluorescence in situ hybridization (FISH) for deletions of CDKN2C.
  • In 78 myeloma cases, we carried out Affymetrix single nucleotide polymorphism mapping and U133 Plus 2.0 expression arrays.
  • RESULTS: By FISH we identified deletion of 1p32.3 (CDKN2C) in 3 of 66 MGUS (4.5%), 4 of 39 SMM (10.3%), and 55 of 369 multiple myeloma cases (15%).
  • CONCLUSIONS: Our results suggest that deletions of CDKN2C are important in the progression and clinical outcome of myeloma.
  • [MeSH-major] Cyclin-Dependent Kinase Inhibitor p18 / genetics. Gene Deletion. Multiple Myeloma / genetics
  • [MeSH-minor] Aged. Cell Line, Tumor. Chromosome Mapping / methods. Disease Progression. Heterozygote. Homozygote. Humans. In Situ Hybridization, Fluorescence. Middle Aged. Models, Genetic. Time Factors. Treatment Outcome

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  • (PMID = 18829482.001).
  • [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 Kingdom / Cancer Research UK / / A6308; United Kingdom / Cancer Research UK / /
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / CDKN2C protein, human; 0 / Cyclin-Dependent Kinase Inhibitor p18
  • [Other-IDs] NLM/ PMC2581792; NLM/ UKMS2612
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54. Katzmann JA, Kyle RA, Benson J, Larson DR, Snyder MR, Lust JA, Rajkumar SV, Dispenzieri A: Screening panels for detection of monoclonal gammopathies. Clin Chem; 2009 Aug;55(8):1517-22
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • Although there are several reports on the relative diagnostic contribution of these assays, none has looked at the tests singly and in combination for the various plasma cell proliferative disorders (PCPDs).
  • METHODS: Patients with a PCPD and all 5 assays performed within 30 days of diagnosis were included (n = 1877).
  • The diagnoses were multiple myeloma (MM) (n = 467), smoldering multiple myeloma (SMM) (n = 191), monoclonal gammopathy of undetermined significance (MGUS) (n = 524), plasmacytoma (n = 29), extramedullary plasmacytoma (n = 10), Waldenström macroglobulinemia (WM) (n = 26), primary amyloidosis (AL) (n = 581), light chain deposition disease (LCDD) (n = 18), and POEMS syndrome (n = 31).

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  • [CommentIn] Clin Chem. 2010 Apr;56(4):677-9; author reply 679-80 [20110450.001]
  • (PMID = 19520758.001).
  • [ISSN] 1530-8561
  • [Journal-full-title] Clinical chemistry
  • [ISO-abbreviation] Clin. Chem.
  • [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 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 / Blood Proteins; 0 / Immunoglobulin Light Chains
  • [Other-IDs] NLM/ NIHMS498187; NLM/ PMC3773468
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55. Zivković SA, Lacomis D, Lentzsch S: Paraproteinemic neuropathy. Leuk Lymphoma; 2009 Sep;50(9):1422-33
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • Paraproteinemic neuropathy (PPN) is most commonly associated with monoclonal gammopathy of undetermined significance, and may also occur in the context of multiple myeloma, amyloidosis, cryoglobulinemia, and other hematologic malignant and nonmalignant conditions.
  • Possible malignant conversion of underlying benign monoclonal gammopathy should be closely monitored, and risk factors include progression of neuropathy and rising titers of monoclonal protein.
  • Therapy is mostly based on the treatment of the underlying hematologic disorder.
  • At this time it is not clear whether mere presence of neuropathy warrants more aggressive treatment of otherwise quiescent hematologic malignances (e.g. smoldering myeloma).

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  • (PMID = 19637090.001).
  • [ISSN] 1029-2403
  • [Journal-full-title] Leukemia & lymphoma
  • [ISO-abbreviation] Leuk. Lymphoma
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
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56. Ross FM, Ibrahim AH, Vilain-Holmes A, Winfield MO, Chiecchio L, Protheroe RK, Strike P, Gunasekera JL, Jones A, Harrison CJ, Morgan GJ, Cross NC, UK Myeloma Forum: Age has a profound effect on the incidence and significance of chromosome abnormalities in myeloma. Leukemia; 2005 Sep;19(9):1634-42
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Age has a profound effect on the incidence and significance of chromosome abnormalities in myeloma.
  • A simple high throughput micro-fluorescence in situ hybridisation technique (FISH) was used to detect chromosome 13 deletions (delta13), immunoglobulin heavy chain (IgH) rearrangements, t(11;14)(q13;q32), t(4;14)(p16;q32), t(14;16)(q23;q32), p53 loss, and numerical changes of chromosomes 3, 6, 7, 9, 10, 11 and 17 in 228 cases of multiple myeloma (MM), including 33 asymptomatic/smouldering MM (SMM).
  • [MeSH-major] Chromosome Aberrations. Multiple Myeloma / genetics

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  • (PMID = 15990862.001).
  • [ISSN] 0887-6924
  • [Journal-full-title] Leukemia
  • [ISO-abbreviation] Leukemia
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
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57. Rajkumar SV, Buadi F: Multiple myeloma: new staging systems for diagnosis, prognosis and response evaluation. Best Pract Res Clin Haematol; 2007 Dec;20(4):665-80
The Lens. Cited by Patents in .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Multiple myeloma: new staging systems for diagnosis, prognosis and response evaluation.
  • Multiple myeloma must be distinguished from monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and several other closely related plasma-cell disorders.
  • In recent years, new systems have emerged for diagnosis, staging, and risk stratification of myeloma.
  • The criteria recommended are primarily derived from the International Myeloma Working Group, with certain updates and clarifications.
  • The International Staging System (ISS) is the standard for staging of myeloma.
  • The International Myeloma Working Group uniform response criteria have been developed as the standard for response assessment in current and future clinical trials.
  • [MeSH-major] Multiple Myeloma / diagnosis. Multiple Myeloma / pathology. Neoplasm Staging / methods

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  • (PMID = 18070712.001).
  • [ISSN] 1521-6926
  • [Journal-full-title] Best practice & research. Clinical haematology
  • [ISO-abbreviation] Best Pract Res Clin Haematol
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA 100080; United States / NCI NIH HHS / CA / CA 107476; United States / NCI NIH HHS / CA / CA 62242; United States / NCI NIH HHS / CA / CA 93842
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Review
  • [Publication-country] England
  • [Number-of-references] 86
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58. Hanamura I, Stewart JP, Huang Y, Zhan F, Santra M, Sawyer JR, Hollmig K, Zangarri M, Pineda-Roman M, van Rhee F, Cavallo F, Burington B, Crowley J, Tricot G, Barlogie B, Shaughnessy JD Jr: Frequent gain of chromosome band 1q21 in plasma-cell dyscrasias detected by fluorescence in situ hybridization: incidence increases from MGUS to relapsed myeloma and is related to prognosis and disease progression following tandem stem-cell transplantation. Blood; 2006 Sep 1;108(5):1724-32
The Lens. Cited by Patents in .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Frequent gain of chromosome band 1q21 in plasma-cell dyscrasias detected by fluorescence in situ hybridization: incidence increases from MGUS to relapsed myeloma and is related to prognosis and disease progression following tandem stem-cell transplantation.
  • Using fluorescence in situ hybridization we investigated amplification of chromosome band 1q21 (Amp1q21) in more than 500 untreated patients with monoclonal gammopathy of undetermined significance (MGUS; n = 14), smoldering multiple myeloma (SMM; n = 31), and newly diagnosed MM (n = 479) as well as 45 with relapsed MM.
  • The proportion of cells with Amp1q21 and the copy number of 1q21 tended to increase at relapse compared with diagnosis.

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  • (PMID = 16705089.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / CA55819; United States / NCI NIH HHS / CA / CA97513
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Other-IDs] NLM/ PMC1895503
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59. Katzmann JA, Abraham RS, Dispenzieri A, Lust JA, Kyle RA: Diagnostic performance of quantitative kappa and lambda free light chain assays in clinical practice. Clin Chem; 2005 May;51(5):878-81
The Lens. Cited by Patents in .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • BACKGROUND: The quantitative assay for free light chains (FLCs) is a recently introduced commercial test reported to be sensitive and specific for detecting FLC diseases such as primary systemic amyloidosis (AL), light chain deposition disease (LCDD), nonsecretory multiple myeloma (NSMM), and light chain multiple myeloma.
  • The majority of these patients (88%) had bone marrow-derived monoclonal plasma cell disorders (PCDs).
  • Among the patients with monoclonal gammopathies were patients with multiple myeloma (330), AL (269), monoclonal gammopathy of undetermined significance (114), smoldering multiple myeloma (72), plasmacytoma (22), NSMM (20), macroglobulinemia (9), LCDD (7), and a variety of other PCDs.
  • Among the 110 AL patients who had not been previously treated and who had a FLC assay performed within 120 days of diagnosis, the FLC kappa/lambda ratio was positive in 91% compared with 69% for serum immunofixation electrophoresis (IFE) and 83% for urine IFE.
  • [MeSH-major] Amyloidosis / diagnosis. Immunoglobulin kappa-Chains / blood. Immunoglobulin lambda-Chains / blood. Paraproteinemias / diagnosis
  • [MeSH-minor] Clinical Laboratory Information Systems. Humans. Laboratories, Hospital. Medical Records Systems, Computerized. Multiple Myeloma / diagnosis. Plasmacytoma / diagnosis. Waldenstrom Macroglobulinemia / diagnosis

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  • [CommentIn] Clin Chem. 2005 May;51(5):805-7 [15855664.001]
  • (PMID = 15774572.001).
  • [ISSN] 0009-9147
  • [Journal-full-title] Clinical chemistry
  • [ISO-abbreviation] Clin. Chem.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA62242
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Immunoglobulin kappa-Chains; 0 / Immunoglobulin lambda-Chains
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60. O'Connell TX, Horita TJ, Kasravi B: Understanding and interpreting serum protein electrophoresis. Am Fam Physician; 2005 Jan 1;71(1):105-12

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • Serum protein electrophoresis is used to identify patients with multiple myeloma and other serum protein disorders.
  • Plasma protein levels display reasonably predictable changes in response to acute inflammation, malignancy, trauma, necrosis, infarction, burns, and chemical injury.
  • Monoclonal gammopathies are associated with a clonal process that is malignant or potentially malignant, including multiple myeloma, Waldenstrom's macroglobulinemia, solitary plasmacytoma, smoldering multiple myeloma, monoclonal gammopathy of undetermined significance, plasma cell leukemia, heavy chain disease, and amyloidosis.
  • The quantity of M protein, the results of bone marrow biopsy, and other characteristics can help differentiate multiple myeloma from the other causes of monoclonal gammopathy.
  • [MeSH-major] Blood Protein Disorders / diagnosis. Blood Protein Electrophoresis / standards

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  • (PMID = 15663032.001).
  • [ISSN] 0002-838X
  • [Journal-full-title] American family physician
  • [ISO-abbreviation] Am Fam Physician
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Number-of-references] 13
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61. Fagerli UM, Holt RU, Holien T, Vaatsveen TK, Zhan F, Egeberg KW, Barlogie B, Waage A, Aarset H, Dai HY, Shaughnessy JD Jr, Sundan A, Børset M: Overexpression and involvement in migration by the metastasis-associated phosphatase PRL-3 in human myeloma cells. Blood; 2008 Jan 15;111(2):806-15
The Lens. Cited by Patents in .

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Overexpression and involvement in migration by the metastasis-associated phosphatase PRL-3 in human myeloma cells.
  • Multiple myeloma (MM) is characterized by accumulation and dissemination of malignant plasma cells (PCs) in the bone marrow (BM).
  • Gene expression profiling of 2 MM cell lines (OH-2 and IH-1) indicated that expression of PRL-3, a metastasis-associated tyrosine phosphatase, was induced by several mitogenic cytokines.
  • Cytokine-driven PRL-3 expression could be shown in several myeloma cell lines at both the mRNA and protein levels.
  • There was significantly higher expression of the PRL-3 gene in PCs from patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma (SMM), and myeloma than in PCs from healthy persons.
  • Silencing of the PRL-3 gene by siRNA reduced cell migration in the MM cell line INA-6, but had no detectable effect on proliferation and cell-cycle phase distribution of the cells.
  • In conclusion, PRL-3 is a gene product specifically expressed in malignant plasma cells and may have a role in migration of these cells.

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  • (PMID = 17934070.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / P01 CA055819; United States / NCI NIH HHS / CA / P01 CA55819
  • [Publication-type] Journal Article; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Cytokines; 0 / Neoplasm Proteins; 0 / RNA, Messenger; 0 / RNA, Neoplasm; EC 3.1.3.48 / PTP4A3 protein, human; EC 3.1.3.48 / Protein Tyrosine Phosphatases
  • [Other-IDs] NLM/ PMC2200854
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62. Mayo MM, Johns GS: Serum free light chains in the diagnosis and monitoring of patients with plasma cell dyscrasias. Contrib Nephrol; 2007;153:44-65
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Serum free light chains in the diagnosis and monitoring of patients with plasma cell dyscrasias.
  • Serum free light chain assay is a recently available test for diagnosis and monitoring of patients with plasma cell dyscrasias.
  • These patients include non-secretory multiple myeloma, amyloidosis and light chain deposition disease.
  • In addition other uses for the test include monitoring response to treatment and earlier detection of relapse in all patients with plasma cell dyscrasias.
  • Potential uses include assessing progression of patients with monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, solitary bone plasmacytoma and extramedullary plasmacytoma to multiple meyloma.
  • [MeSH-major] Immunoglobulin Light Chains / blood. Paraproteinemias / blood. Paraproteinemias / diagnosis
  • [MeSH-minor] Amyloidosis / blood. Amyloidosis / diagnosis. Amyloidosis / immunology. Bence Jones Protein / analysis. Disease Progression. Humans. Multiple Myeloma / blood. Multiple Myeloma / diagnosis. Multiple Myeloma / immunology. Plasmacytoma / blood. Plasmacytoma / diagnosis. Plasmacytoma / immunology

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  • (PMID = 17075223.001).
  • [ISSN] 0302-5144
  • [Journal-full-title] Contributions to nephrology
  • [ISO-abbreviation] Contrib Nephrol
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] Switzerland
  • [Chemical-registry-number] 0 / Immunoglobulin Light Chains; 9006-99-9 / Bence Jones Protein
  • [Number-of-references] 77
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63. Gonzalez-Paz N, Chng WJ, McClure RF, Blood E, Oken MM, Van Ness B, James CD, Kurtin PJ, Henderson K, Ahmann GJ, Gertz M, Lacy M, Dispenzieri A, Greipp PR, Fonseca R: Tumor suppressor p16 methylation in multiple myeloma: biological and clinical implications. Blood; 2007 Feb 1;109(3):1228-32
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Tumor suppressor p16 methylation in multiple myeloma: biological and clinical implications.
  • The biological and clinical implications of p16 gene methylation in multiple myeloma (MM) are still unclear despite previous studies.
  • In this comprehensive study, using methylation-specific PCR (MS-PCR), we show that p16 methylation is relatively common and occurs in monoclonal gammopathy of undetermined significance (MGUS; n=17), smoldering multiple myeloma (SMM; n=40), and MM (n=522) at a prevalence of 24%, 28%, and 34%, respectively.
  • In addition, p16 methylation has no apparent effect on the cycle because there was also no difference in the plasma cell labeling index (a direct measurement of proliferation) between patients with and without p16 methylation.
  • Our results question a major role for p16 methylation in the oncogenesis of the PC neoplasm, and we now believe p16 methylation may be a marker for overall epigenetic changes associated with disease progression, with no obvious direct biological or clinical consequences.
  • [MeSH-major] DNA Methylation. Genes, p16. Multiple Myeloma / genetics
  • [MeSH-minor] Cell Cycle. Disease Progression. Epigenesis, Genetic. Humans. Middle Aged. Survival Rate. Tumor Suppressor Proteins / genetics

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  • [CommentIn] Blood. 2007 Feb 1;109(3):1337-8 [17244692.001]
  • (PMID = 16840723.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / CA21115-25C; United States / NCI NIH HHS / CA / P01 CA100707-01; 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 / Tumor Suppressor Proteins
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64. Katzmann JA, Dispenzieri A, Kyle RA, Snyder MR, Plevak MF, Larson DR, Abraham RS, Lust JA, Melton LJ 3rd, Rajkumar SV: Elimination of the need for urine studies in the screening algorithm for monoclonal gammopathies by using serum immunofixation and free light chain assays. Mayo Clin Proc; 2006 Dec;81(12):1575-8
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • PATIENTS AND METHODS: We identified 428 patients with a monoclonal gammopathy and monoclonal urinary protein at initial diagnosis of plasma cell dyscrasia who had also undergone serum immunofixation and serum free light chain quantitation within 30 days of diagnosis.
  • RESULTS: The patients had diagnoses of multiple myeloma, primary amyloid, monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, solitary plasmacytomas, and other less frequently detected monoclonal gammopathies.
  • [MeSH-major] Immunoglobulin Light Chains / blood. Paraproteinemias / diagnosis. Urinalysis
  • [MeSH-minor] Algorithms. Diagnosis, Differential. Diagnostic Errors. Electrophoresis. Humans. Proteinuria

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  • (PMID = 17165636.001).
  • [ISSN] 0025-6196
  • [Journal-full-title] Mayo Clinic proceedings
  • [ISO-abbreviation] Mayo Clin. Proc.
  • [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
  • [Chemical-registry-number] 0 / Immunoglobulin Light Chains
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65. Kline M, Donovan K, Wellik L, Lust C, Jin W, Moon-Tasson L, Xiong Y, Witzig TE, Kumar S, Rajkumar SV, Lust JA: Cytokine and chemokine profiles in multiple myeloma; significance of stromal interaction and correlation of IL-8 production with disease progression. Leuk Res; 2007 May;31(5):591-8
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Cytokine and chemokine profiles in multiple myeloma; significance of stromal interaction and correlation of IL-8 production with disease progression.
  • Multiple myeloma (MM) is a product of interactions between tumor plasma cells and multiple cell types native to the bone marrow (BM).
  • We have used antibody array technology to examine the proteins produced by BM stromal cells in response to stimulation by BM taken from patients diagnosed with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and MM.
  • We observed increased production of the chemokine IL-8 by stromal cells co-cultured with supernatants from bone marrow cells of patients with active myeloma.
  • Consistent with the pro-angiogenic activity of IL-8, increased BM microvessel density (MVD) correlated with stimulation of stromal cell IL-8 production.
  • In addition, the majority of MM cell lines and MM patient plasma cells were found to express IL-8 receptors CXCR1 and CXCR2.
  • We conclude that stromal cell IL-8 production parallels MM disease activity, is IL-1beta induced, and correlates with bone marrow angiogenesis.
  • [MeSH-major] Bone Marrow / metabolism. Chemokines / metabolism. Interleukin-8 / metabolism. Multiple Myeloma / metabolism. Paraproteinemias / metabolism

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  • (PMID = 16879867.001).
  • [ISSN] 0145-2126
  • [Journal-full-title] Leukemia research
  • [ISO-abbreviation] Leuk. Res.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Chemokines; 0 / Interleukin-1beta; 0 / Interleukin-8; 0 / NF-kappa B; 0 / Receptors, Interleukin-8
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66. Sanders J, Crawford B, Gibson J, Joy Ho P, Iland H, Joshua D: Is there a case for the early use of bisphosphonates in smouldering myeloma and MGUS? (Bisphosphonates in SMM & MGUS). Int J Lab Hematol; 2007 Oct;29(5):395-7
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Is there a case for the early use of bisphosphonates in smouldering myeloma and MGUS? (Bisphosphonates in SMM & MGUS).
  • [MeSH-major] Bone Density Conservation Agents / therapeutic use. Diphosphonates / therapeutic use. Imidazoles / therapeutic use. Multiple Myeloma / complications. Osteoporosis / drug therapy. Paraproteinemias / complications

  • MedlinePlus Health Information. consumer health - Multiple Myeloma.
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  • (PMID = 17824924.001).
  • [ISSN] 1751-5521
  • [Journal-full-title] International journal of laboratory hematology
  • [ISO-abbreviation] Int J Lab Hematol
  • [Language] eng
  • [Publication-type] Clinical Trial; Letter; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Bone Density Conservation Agents; 0 / Diphosphonates; 0 / Imidazoles; 6XC1PAD3KF / zoledronic acid
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67. Sorli ML, Gimeno E, Abella E, Besses C, Knobel H: Smoldering myeloma in HIV patient: a complete remission after antiretroviral therapy. Leuk Res; 2008 Sep;32(9):1482-3
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Smoldering myeloma in HIV patient: a complete remission after antiretroviral therapy.
  • [MeSH-major] Antiretroviral Therapy, Highly Active. HIV Infections / drug therapy. Multiple Myeloma / drug therapy


68. Filanovsky K, Lev S, Haran M, Feldberg E, Bassous L, Berrebi A, Shtalrid M: Systemic mastocytosis associated with smoldering multiple myeloma: an unexpected diagnosis in a patient with a rash. Leuk Lymphoma; 2010 Jun;51(6):1152-4
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  • [Title] Systemic mastocytosis associated with smoldering multiple myeloma: an unexpected diagnosis in a patient with a rash.
  • [MeSH-major] Exanthema / complications. Mastocytosis, Systemic / diagnosis. Multiple Myeloma / diagnosis
  • [MeSH-minor] Aged. Diagnosis, Differential. Humans. Male


69. Andrews AT: Smoldering multiple myeloma. N Engl J Med; 2007 Sep 6;357(10):1048; author reply 1049-50
MedlinePlus Health Information. consumer health - Multiple Myeloma.

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Smoldering multiple myeloma.
  • [MeSH-major] Immunoglobulin A. Multiple Myeloma / immunology

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  • [CommentOn] N Engl J Med. 2007 Jun 21;356(25):2582-90 [17582068.001]
  • (PMID = 17823991.001).
  • [ISSN] 1533-4406
  • [Journal-full-title] The New England journal of medicine
  • [ISO-abbreviation] N. Engl. J. Med.
  • [Language] eng
  • [Publication-type] Comment; Letter
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Immunoglobulin A; 0 / Immunoglobulin G
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70. Prasad HK, Zhan F, Shaughnessy J: Smoldering multiple myeloma. N Engl J Med; 2007 Sep 6;357(10):1048; author reply 1049-50
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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.
  • [MeSH-major] Gene Expression Profiling. Multiple Myeloma / genetics

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  • [CommentOn] N Engl J Med. 2007 Jun 21;356(25):2582-90 [17582068.001]
  • (PMID = 17804853.001).
  • [ISSN] 1533-4406
  • [Journal-full-title] The New England journal of medicine
  • [ISO-abbreviation] N. Engl. J. Med.
  • [Language] eng
  • [Publication-type] Comment; Letter
  • [Publication-country] United States
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71. Focosi D: Smoldering multiple myeloma. N Engl J Med; 2007 Sep 6;357(10):1048-9; author reply 1049-50
MedlinePlus Health Information. consumer health - Multiple Myeloma.

  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Smoldering multiple myeloma.
  • [MeSH-major] Anemia / etiology. Magnetic Resonance Imaging. Multiple Myeloma / diagnosis

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  • [CommentOn] N Engl J Med. 2007 Jun 21;356(25):2582-90 [17582068.001]
  • (PMID = 17823992.001).
  • [ISSN] 1533-4406
  • [Journal-full-title] The New England journal of medicine
  • [ISO-abbreviation] N. Engl. J. Med.
  • [Language] eng
  • [Publication-type] Comment; Letter
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Hemoglobins
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72. Cortesão E, Espadana A, Laranjeiro P, Jara M, Orfão A: Successful treatment with VAD of a myelodysplastic syndrome occurring during the course of a smoldering multiple myeloma. Leuk Res; 2009 Jan;33(1):195-7
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Successful treatment with VAD of a myelodysplastic syndrome occurring during the course of a smoldering multiple myeloma.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Multiple Myeloma / drug therapy






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