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1. Choi YL, Park JH, Kim WS, Lee DY, Lee JH, Yang JM, Lee ES: Aggressive NK-cell leukaemia associated with reactive haemophagocytic syndrome. Clin Exp Dermatol; 2006 Jan;31(1):83-5
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  • [Title] Aggressive NK-cell leukaemia associated with reactive haemophagocytic syndrome.
  • We report a case of aggressive NK-cell leukaemia associated with reactive haemophagocytic syndrome in a 29-year-old Korean woman who had several small purpuric patches on both thighs.
  • Laboratory tests revealed pancytopenia and deranged liver function, and atypical lymphocytes containing toxic granules were detected from peripheral blood and bone marrow.
  • [MeSH-major] Killer Cells, Natural / immunology. Leukemia / immunology. Lymphohistiocytosis, Hemophagocytic / immunology. Lymphoma, T-Cell, Cutaneous / immunology

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  • (PMID = 16309492.001).
  • [ISSN] 0307-6938
  • [Journal-full-title] Clinical and experimental dermatology
  • [ISO-abbreviation] Clin. Exp. Dermatol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antigens, CD
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2. Moubayed P, Leithäuser F, Binder T, Uppenkamp M, Feller AC: Two cases of primary malignant NK/T-cell lymphoma in the small intestine following an aggressive clinical course: Morphological, immunohistochemical, and molecular analysis. Leuk Lymphoma; 2007 Jul;48(7):1451-5
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  • [Title] Two cases of primary malignant NK/T-cell lymphoma in the small intestine following an aggressive clinical course: Morphological, immunohistochemical, and molecular analysis.
  • [MeSH-major] Ileal Neoplasms / diagnosis. Killer Cells, Natural / pathology. Lymphoma, T-Cell / diagnosis
  • [MeSH-minor] Adult. Aged. Cell Shape. Humans. Immunohistochemistry. Immunophenotyping. Male

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  • (PMID = 17613782.001).
  • [ISSN] 1042-8194
  • [Journal-full-title] Leukemia & lymphoma
  • [ISO-abbreviation] Leuk. Lymphoma
  • [Language] eng
  • [Publication-type] Case Reports; Letter
  • [Publication-country] England
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3. Osuji N, Matutes E, Catovsky D, Lampert I, Wotherspoon A: Histopathology of the spleen in T-cell large granular lymphocyte leukemia and T-cell prolymphocytic leukemia: a comparative review. Am J Surg Pathol; 2005 Jul;29(7):935-41
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  • [Title] Histopathology of the spleen in T-cell large granular lymphocyte leukemia and T-cell prolymphocytic leukemia: a comparative review.
  • We review retrospectively the spleen histology in 8 patients with T-cell large granular lymphocyte (LGL) leukemia and 4 with T-cell prolymphocytic leukemia (T-PLL) to identify characteristic patterns of involvement and to distinguish such patterns from those described in other low grade B- and T-cell malignancies.
  • Moderate splenic enlargement with red pulp expansion due to lymphocytic infiltration was characteristic of LGL leukemia.
  • Abnormal lymphocytes expressed cytotoxic granule proteins and were consistently CD45RO and CD5 negative in contrast to normal red pulp T cells.
  • Unlike in hairy cell leukemia, the main differential diagnosis for red pulp lymphocytosis, the white pulp was not only preserved in T-cell LGL leukemia but showed germinal center hyperplasia with expansion of the mantle zones.
  • T-PLL lymphocytes, unlike LGLs, were more invasive, infiltrating the spleen capsule as well as white pulp areas.
  • T-cell prolymphocytes did not express cytotoxic granule proteins or NK-cell markers, were CD5+, CD45RO+ like normal spleen T cells, were CD2+, CD3+, CD45+, CD43+, TCRbeta+, but CD25-, CD30-, ALK-1-, TRAP-, DBA44-, and TdT-.
  • These observations on the morphologic and immunohistochemical appearances of the spleen in T-cell LGL leukemia and T-PLL may aid diagnosis of these uncommon T-cell disorders, particularly T-cell LGL leukemia, where presentation may be cryptic and where unique pathognomonic features, are absent.
  • [MeSH-major] Leukemia, Prolymphocytic / pathology. Leukemia, T-Cell / pathology. Spleen / pathology
  • [MeSH-minor] Adolescent. Adult. Aged. Biomarkers, Tumor / analysis. Diagnosis, Differential. Female. Humans. Immunohistochemistry. Lymphocytes / metabolism. Lymphocytes / pathology. Male. Middle Aged. Retrospective Studies

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  • (PMID = 15958859.001).
  • [ISSN] 0147-5185
  • [Journal-full-title] The American journal of surgical pathology
  • [ISO-abbreviation] Am. J. Surg. Pathol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Biomarkers, Tumor
  • [Number-of-references] 23
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4. Shah MV, Zhang R, Irby R, Kothapalli R, Liu X, Arrington T, Frank B, Lee NH, Loughran TP Jr: Molecular profiling of LGL leukemia reveals role of sphingolipid signaling in survival of cytotoxic lymphocytes. Blood; 2008 Aug 1;112(3):770-81
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  • [Title] Molecular profiling of LGL leukemia reveals role of sphingolipid signaling in survival of cytotoxic lymphocytes.
  • T-cell large granular lymphocyte (LGL) leukemia is characterized by clonal expansion of CD3(+)CD8(+) cells.
  • Leukemic LGLs correspond to terminally differentiated effector-memory cytotoxic T lymphocytes (CTLs) that escape Fas-mediated activation-induced cell death (AICD) in vivo.
  • The gene expression signature of peripheral blood mononuclear cells from 30 LGL leukemia patients showed profound dysregulation of expression of apoptotic genes and suggested uncoupling of activation and apoptotic pathways as a mechanism for failure of AICD in leukemic LGLs.
  • Therapeutic targeting of this pathway, such as use of FTY720, may have efficacy in LGL leukemia.

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  • (PMID = 18477771.001).
  • [ISSN] 1528-0020
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / R01 CA090633; United States / NCI NIH HHS / CA / R01 CA098472; United States / NCI NIH HHS / CA / CA90633; United States / NCI NIH HHS / CA / CA94872
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Receptors, Lysosphingolipid; 0 / Sphingolipids; EC 3.2.1.47 / Galactosylgalactosylglucosylceramidase
  • [Other-IDs] NLM/ PMC2481553
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5. Malani AK, Gupta C, Rangineni R, Singh J, Ammar H: Concomitant presentation of acute myeloid leukemia with T-cell large granular lymphocytic leukemia. Acta Oncol; 2007;46(2):247-9
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  • [Title] Concomitant presentation of acute myeloid leukemia with T-cell large granular lymphocytic leukemia.
  • T-cell large granular lymphocyte leukemia (T-LGL) also known as T-cell chronic lymphocytic leukemia is rare and comprises a small minority of all small lymphocytic leukemias.
  • The concomitant presentation of T-LGL with acute myeloid leukemia (AML) has not been previously reported.
  • We present an elderly gentleman with concomitant T-LGL and AML (non-M3) diagnosed by a combination of morphologic evaluation, immunophenotyping by flow cytometry, and T-cell gene rearrangement studies.
  • He remains alive and well seven months after initial diagnosis.
  • [MeSH-major] Leukemia, Myeloid / diagnosis. Leukemia, Prolymphocytic, T-Cell / diagnosis
  • [MeSH-minor] Acute Disease. Aged, 80 and over. Antigens, CD / analysis. Flow Cytometry. Humans. Male

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  • (PMID = 17453377.001).
  • [ISSN] 0284-186X
  • [Journal-full-title] Acta oncologica (Stockholm, Sweden)
  • [ISO-abbreviation] Acta Oncol
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Review
  • [Publication-country] Norway
  • [Chemical-registry-number] 0 / Antigens, CD
  • [Number-of-references] 17
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6. Robak T: Novel drugs for chronic lymphoid leukemias: mechanism of action and therapeutic activity. Curr Med Chem; 2009;16(18):2212-34
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  • [Title] Novel drugs for chronic lymphoid leukemias: mechanism of action and therapeutic activity.
  • Chronic lymphoid leukemias include well defined mature B-cell and T-cell neoplasms with diverse natural history and specific morphological, immunophenotypic and molecular characteristics.
  • The most common adult leukemia in the Western world is chronic lymphocytic leukemia (CLL).
  • Rarer indolent lymphoid leukemias include prolymphocytic leukemia, hairy cell leukemia, large granular lymphocyte leukemia and T-cell leukemia/lymphoma.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Drug Design. Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy

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  • (PMID = 19519388.001).
  • [ISSN] 0929-8673
  • [Journal-full-title] Current medicinal chemistry
  • [ISO-abbreviation] Curr. Med. Chem.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] Netherlands
  • [Chemical-registry-number] 0 / Antineoplastic Agents
  • [Number-of-references] 230
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7. Kwong YL: Association of T-cell large granular lymphocytic leukaemia with autologous haematopoietic stem cell transplantation: real or fortuitous. Bone Marrow Transplant; 2005 Mar;35(6):625
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  • [Title] Association of T-cell large granular lymphocytic leukaemia with autologous haematopoietic stem cell transplantation: real or fortuitous.
  • [MeSH-major] Hematopoietic Stem Cell Transplantation / adverse effects. Leukemia, T-Cell / etiology
  • [MeSH-minor] Cell Proliferation / drug effects. Humans. Immunosuppression / adverse effects. Transplantation, Autologous

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  • (PMID = 15640811.001).
  • [ISSN] 0268-3369
  • [Journal-full-title] Bone marrow transplantation
  • [ISO-abbreviation] Bone Marrow Transplant.
  • [Language] eng
  • [Publication-type] Letter
  • [Publication-country] England
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8. O'Malley DP: T-cell large granular leukemia and related proliferations. Am J Clin Pathol; 2007 Jun;127(6):850-9
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  • [Title] T-cell large granular leukemia and related proliferations.
  • Session 9 of the 2005 Society for Hematopathology/European Association for Haematopathology Workshop focused on large granular lymphocyte (LGL) leukemias and related disorders.
  • T-cell LGL (T-LGL) leukemias, discussed herein, account for 2% to 3% of cases of small lymphocytic leukemia.
  • T-LGL diseases cover a heterogeneous spectrum of disorders that include reactive conditions, typically associated with autoimmune disease, to outright leukemia.
  • These disorders are found in older people, with an average age at initial examination of approximately 60 years and a median survival of more than 10 years in T-LGL leukemia.
  • Lymphocytosis, composed of small mature lymphocytes with increased cytoplasm, is common.
  • The spleen and bone marrow are involved in T-LGL leukemia, although morphologic findings may be subtle.
  • Some cases may be due to chronic immune stimulation, with subsequent clonal escape and proliferation of a neoplastic population of lymphocytes.
  • [MeSH-major] Leukemia, Lymphoid / pathology. T-Lymphocytes / pathology
  • [MeSH-minor] Bone Marrow / pathology. Flow Cytometry. Humans. Immunophenotyping. Lymphocytosis / complications. Lymphocytosis / pathology. Middle Aged. Neutropenia / complications. Neutropenia / pathology. Spleen / pathology

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  • (PMID = 17509982.001).
  • [ISSN] 0002-9173
  • [Journal-full-title] American journal of clinical pathology
  • [ISO-abbreviation] Am. J. Clin. Pathol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Number-of-references] 57
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9. Scquizzato E, Teramo A, Miorin M, Facco M, Piazza F, Noventa F, Trentin L, Agostini C, Zambello R, Semenzato G: Genotypic evaluation of killer immunoglobulin-like receptors in NK-type lymphoproliferative disease of granular lymphocytes. Leukemia; 2007 May;21(5):1060-9
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  • [Title] Genotypic evaluation of killer immunoglobulin-like receptors in NK-type lymphoproliferative disease of granular lymphocytes.
  • Using polymerase chain reaction (PCR)-based sequence-specific primers, the killer immunoglobulin-like receptor (KIR) genotypes of 35 patients with natural killer (NK)-type lymphoproliferative disease of granular lymphocytes and of 50 normal subjects were investigated to evaluate whether genes coding for activating KIRs were more frequently detected in patients with NK-lymphoproliferative disease of granular lymphocytes (LDGL).
  • KIR gene repertoire analysis in patients suggests that the susceptibility to NK-LDGL might be related to the presence of activating KIR genes and supports the concept that these receptors may be involved in the priming of granular lymphocytes (GL) proliferation.
  • Population analysis might disclose a genetic background predisposing to this disease.
  • [MeSH-major] Killer Cells, Natural / pathology. Lymphoproliferative Disorders / immunology. Receptors, Immunologic / genetics

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  • (PMID = 17361229.001).
  • [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
  • [Chemical-registry-number] 0 / KIR2DL5A protein, human; 0 / Receptors, Immunologic; 0 / Receptors, KIR; 0 / Receptors, KIR2DL5
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10. Petterson TE, Bosco AA, Cohn RJ: Aggressive natural killer cell leukemia presenting with hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer; 2008 Mar;50(3):654-7
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  • [Title] Aggressive natural killer cell leukemia presenting with hemophagocytic lymphohistiocytosis.
  • Aggressive natural killer cell leukemia (ANKL) is a very rare condition and when reported occurs almost exclusively in adults.
  • We report a pediatric case of ANKL that presented with hemophagocytic syndrome, preceding the onset of leukemia by 12 weeks.
  • [MeSH-major] Leukemia, Large Granular Lymphocytic / complications. Lymphohistiocytosis, Hemophagocytic / etiology
  • [MeSH-minor] Aneuploidy. Antigens, CD8 / analysis. Child, Preschool. Chromosome Aberrations. Chromosomes, Human, Pair 6 / ultrastructure. Chromosomes, Human, Pair 7 / ultrastructure. Disease Progression. Epstein-Barr Virus Infections / complications. Fatal Outcome. Humans. Male. Multiple Organ Failure / etiology. Opportunistic Infections / etiology

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  • [Copyright] (c) 2007 Wiley-Liss, Inc.
  • (PMID = 17853464.001).
  • [ISSN] 1545-5017
  • [Journal-full-title] Pediatric blood & cancer
  • [ISO-abbreviation] Pediatr Blood Cancer
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antigens, CD8
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11. Tanaka Y, Matsui K, Yamashita K, Matsuda K, Shinohara K, Matsutani A: T-gamma delta large granular lymphocyte leukemia preceded by pure red cell aplasia and complicated with hemophagocytic syndrome caused by Epstein-Barr virus infection. Intern Med; 2006;45(9):631-5
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  • [Title] T-gamma delta large granular lymphocyte leukemia preceded by pure red cell aplasia and complicated with hemophagocytic syndrome caused by Epstein-Barr virus infection.
  • A 51-year-old man developed anemia, and was diagnosed with pure red cell aplasia through the absence of erythroid progenitors.
  • Large granular lymphocyte (LGL) leukemia with the T-cell gamma delta phenotype evolved after 6 months showing CD2+, CD3+, CD8- and CD56- with the T-cell receptor beta gene rearrangement, clonalities of gamma and delta genes and complex chromosome abnormality simultaneously with hemophagocytic syndrome (HPS).
  • In the present patient, it seemed that lymphoproliferative disease of large granular lymphocytes (LDGL) manifested initially as PRCA, gammadelta LGL leukemia evolved, and finally fatal HPS become complicated, presumably caused by the EBV reactivation in the immunodeficiency state with the administration of immunosuppressants.
  • [MeSH-major] Epstein-Barr Virus Infections / complications. Leukemia, Lymphoid / complications. Lymphocytes / metabolism. Lymphohistiocytosis, Hemophagocytic / complications. Lymphohistiocytosis, Hemophagocytic / virology. Receptors, Antigen, T-Cell, gamma-delta / metabolism. Red-Cell Aplasia, Pure / complications


12. Kawamata N, Inagaki N, Mizumura S, Sugimoto KJ, Sakajiri S, Ohyanagi-Hara M, Oshimi K: Methylation status analysis of cell cycle regulatory genes (p16INK4A, p15INK4B, p21Waf1/Cip1, p27Kip1 and p73) in natural killer cell disorders. Eur J Haematol; 2005 May;74(5):424-9
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  • [Title] Methylation status analysis of cell cycle regulatory genes (p16INK4A, p15INK4B, p21Waf1/Cip1, p27Kip1 and p73) in natural killer cell disorders.
  • Natural killer (NK) cell disorders are rare diseases.
  • In this study we analyze the methylation status of the genes associated with cell cycle regulation, including p16INK4A, p15INK4B, p21/Waf1/Cip1, p27/Kip1, p73, and p14ARF, by methylation specific (MS) PCR and/or bisulfite sequencing.
  • We examined 29 cases of NK cell disorders (five aggressive NK cell leukemia/lymphoma, three blastic NK cell lymphoma/leukemia, five nasal NK cell lymphoma, three myeloid/NK cell precursor acute leukemia, 13 chronic NK lymphocytosis).
  • We found methylation of the first exon of the p16INK4A gene in two cases (one aggressive, one blastic), and methylation of the p14ARF gene in one aggressive NK cell leukemia.
  • MS-PCR suggested that the p73 and p21 genes were methylated in seven cases, respectively (p73: one blastic, one nasal, five chronic; p21: one myeloid/NK, one aggressive, one nasal, and four chronic); bisulfite sequencing confirmed that methylated alleles of these genes were dominant in the samples except three cases (one myeloid/NK, one aggressive, and one chronic) in which methylated alleles of the p21 genes were less than 34% of all alleles.
  • These results suggested that inactivation of the cell cycle regulatory genes by DNA methylation could be associated with tumorigenesis in NK cell disorders, not only aggressive subtypes but also chronic subtype.
  • [MeSH-major] Cell Cycle / genetics. Cell Cycle Proteins / genetics. Cyclin-Dependent Kinase Inhibitor p16 / genetics. DNA Methylation. DNA-Binding Proteins / genetics. Killer Cells, Natural / physiology. Leukemia / genetics. Lymphoma / genetics. Nuclear Proteins / genetics. Tumor Suppressor Proteins / genetics
  • [MeSH-minor] Base Sequence. Chronic Disease. Cyclin-Dependent Kinase Inhibitor p15. Cyclin-Dependent Kinase Inhibitor p21. DNA Primers. Genes, Tumor Suppressor. Humans

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  • (PMID = 15813917.001).
  • [ISSN] 0902-4441
  • [Journal-full-title] European journal of haematology
  • [ISO-abbreviation] Eur. J. Haematol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Denmark
  • [Chemical-registry-number] 0 / CDKN1A protein, human; 0 / CDKN2B protein, human; 0 / Cell Cycle Proteins; 0 / Cyclin-Dependent Kinase Inhibitor p15; 0 / Cyclin-Dependent Kinase Inhibitor p16; 0 / Cyclin-Dependent Kinase Inhibitor p21; 0 / DNA Primers; 0 / DNA-Binding Proteins; 0 / Nuclear Proteins; 0 / Tumor Suppressor Proteins; 0 / tumor suppressor protein p73
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13. Franco G, Palazzolo R, Liardo E, Tripodo C, Mancuso S: T cell large granular lymphocytic leukemia in association with Sjögren's syndrome. Acta Haematol; 2010;124(1):5-8
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  • [Title] T cell large granular lymphocytic leukemia in association with Sjögren's syndrome.
  • T cell large granular lymphocytic (LGL) leukemia is a rare condition accounting for 2-3% of all mature lymphoid leukemias.
  • Hematological assessment revealed the presence of a T cell LGL leukemia.
  • At the time of T cell LGL leukemia diagnosis, the patient developed xerophthalmia and xerostomia, and a diagnosis of Sjögren's syndrome was made following salivary gland biopsy.
  • The finding of large granular lymphocytes in the context of autoimmune disorders is well-known, though it often occurs with rheumatoid arthritis or in association with a positive autoantibody titer in the absence of an overt clinical picture.
  • The concomitant presentation of T cell LGL leukemia with Sjögren's syndrome is a rare event which is worth reporting.
  • [MeSH-major] Leukemia, Large Granular Lymphocytic / complications. Sjogren's Syndrome / complications

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  • [Copyright] Copyright 2010 S. Karger AG, Basel.
  • (PMID = 20501987.001).
  • [ISSN] 1421-9662
  • [Journal-full-title] Acta haematologica
  • [ISO-abbreviation] Acta Haematol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Switzerland
  • [Chemical-registry-number] 0 / Immunosuppressive Agents
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14. Mohan SR, Clemente MJ, Afable M, Cazzolli HN, Bejanyan N, Wlodarski MW, Lichtin AE, Maciejewski JP: Therapeutic implications of variable expression of CD52 on clonal cytotoxic T cells in CD8+ large granular lymphocyte leukemia. Haematologica; 2009 Oct;94(10):1407-14
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  • [Title] Therapeutic implications of variable expression of CD52 on clonal cytotoxic T cells in CD8+ large granular lymphocyte leukemia.
  • BACKGROUND: T-cell large granular lymphocytic leukemia is a clonal proliferation of cytotoxic T-lymphocytes which often results in severe cytopenia.
  • Current treatment options favor chronic immunosuppression.
  • DESIGN AND METHODS: We retrospectively examined treatment outcomes in 59 patients with CD8+ T-cell large granular lymphocytic leukemia, 41 of whom required therapy.
  • Flow cytometry was used to monitor expression of glycophosphatidylinositol-anchored CD52, CD55, and CD59 as well as to characterize T-cell clonal expansions by T-cell receptor variable beta-chain (Vbeta) repertoire.
  • RESULTS: Analysis of the effects of alemtuzumab revealed remissions with restoration of platelets in one of one patient, red blood cell transfusion independence in three of five patients and improvement of neutropenia in one of three, resulting in an overall response rate of 50% (4/8 patients).
  • Clonal large granular lymphocytes exhibited decreased CD52 expression post-therapy in patients refractory to treatment.
  • Samples of large granular lymphocytes collected prior to therapy also unexpectedly had a significant proportion of CD52-negative cells while a healthy control population had no such CD52 deficiency (p=0.026).
  • CONCLUSIONS: While alemtuzumab may be highly effective in large granular lymphocytic leukemia, prospective serial monitoring for the presence of CD52-deficient clonal cytotoxic T-lymphocytes should be a component of clinical trials investigating the efficacy of this drug.
  • CD52 deficiency may explain lack of response to alemtuzumab, and such therapy may confer a survival advantage to glycophosphatidylinositol-negative clonal cytotoxic T-lymphocytes.

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  • [CommentIn] Haematologica. 2009 Oct;94(10):1341-5 [19794080.001]
  • (PMID = 19794084.001).
  • [ISSN] 1592-8721
  • [Journal-full-title] Haematologica
  • [ISO-abbreviation] Haematologica
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / R01 CA113972; United States / NCRR NIH HHS / RR / U54 RR019397; United States / NCRR NIH HHS / RR / U54 RR 019397
  • [Publication-type] Comparative Study; Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] Italy
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / Antibodies, Neoplasm; 0 / Antigens, CD; 0 / Antigens, Neoplasm; 0 / CD52 antigen; 0 / Glycoproteins; 3A189DH42V / alemtuzumab
  • [Other-IDs] NLM/ PMC2754957
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15. Dincol G, Diz-Kuçukkaya R, Bicakci E: T-cell large granular lymphocytic leukaemia: successful response to 2-deoxycoformycin. Neth J Med; 2008 Feb;66(2):85-7
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  • [Title] T-cell large granular lymphocytic leukaemia: successful response to 2-deoxycoformycin.
  • We report a 25-year-old woman with T-cell large granular lymphocytic leukaemia presenting with severe neutropenia, anaemia and recurrent infections with a chronic disease course.
  • Immunophenotyping showed an expansion of CD3+, TCRgamma delta+, CD4-, CD5+, CD7+, CD8+, CD57+ large granular lymphocytes.
  • Finally, treatment with 2-deoxycoformycin resulted in both clinical and haemotological complete responses, despite molecular evidence of the persistence of the abnormal T-cell clone.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Leukemia, Large Granular Lymphocytic / drug therapy. Pentostatin / therapeutic use

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  • (PMID = 18292613.001).
  • [ISSN] 0300-2977
  • [Journal-full-title] The Netherlands journal of medicine
  • [ISO-abbreviation] Neth J Med
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Netherlands
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 395575MZO7 / Pentostatin
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16. Warnnissorn N, Kanitsap N, Kulkantrakorn K, Assanasen T: Natural killer cell malignancy associated with Epstein-Barr virus and hemophagocytic syndrome. J Med Assoc Thai; 2007 May;90(5):982-7
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  • [Title] Natural killer cell malignancy associated with Epstein-Barr virus and hemophagocytic syndrome.
  • Natural killer cell malignancy is a rare and aggressive lymphoid neoplasm encompassing extra-nodal NK/T-cell lymphoma, nasal-type (ENKLN) and aggressive NK-cell lymphoma/leukemia (ANKL).
  • While that of ANKL are medium to large-sized mononuclear cells with moderate cytoplasm.
  • Ancillary techniques studied on paraffin embedded tissues of both cases demonstrated that the neoplastic cells exhibit cytoplasmic CD3+, CD56+ and cytotoxic granules + by immunohistochemistry, absence of T cell receptor gene rearrangement by PCR, and presence of Epstein-Barr virus mRNA (EBER) transcripts by in situ hybridization.
  • The authors reviewed the literature on natural killer cell neoplasm and compared the clinical characteristics, natural history, and association of Epstein-Barr virus infection with hemophagocytic syndrome.
  • [MeSH-major] Epstein-Barr Virus Infections / physiopathology. Killer Cells, Natural / pathology. Leukemia / pathology. Lymphohistiocytosis, Hemophagocytic / physiopathology. Lymphoma / pathology


17. Sawada A, Sato E, Koyama M, Higuchi B, Kusuki S, Kim JY, Takeshita Y, Sakata A, Sakata N, Okamura T, Yasui M, Inoue M, Kawa K: NK-cell repertoire is feasible for diagnosing Epstein-Barr virus-infected NK-cell lymphoproliferative disease and evaluating the treatment effect. Am J Hematol; 2006 Aug;81(8):576-81
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  • [Title] NK-cell repertoire is feasible for diagnosing Epstein-Barr virus-infected NK-cell lymphoproliferative disease and evaluating the treatment effect.
  • Epstein-Barr virus (EBV) occasionally infects T and NK cells and causes EBV-infected T/NK-cell lymphoproliferative disease (LPD), which comprises chronic active EBV infection, EBV-associated hemophagocytic syndrome, mosquito allergy, hydroa vacciniforme, aggressive NK-cell leukemia, and NK/T-cell lymphoma.
  • The diagnosis is proven by the monoclonal proliferation of EBV-infected T or NK cells, which is a time-consuming and complicated method.
  • T-cell monoclonality is helpful for the screening of EBV-infected T-cell LPD in patients with EBV-genome burden and is easily shown with T-cell-receptor rearrangement or the T-cell repertoire, whereas NK-cell monoclonality is difficult to prove due to its lacking such rearranged receptors.
  • We investigated a set of killer immunoglobulin-like receptors (KIRs) and also CD94-NKG2 heterodimers on NK cells, namely the NK-cell repertoire.
  • Skewed repertoires were seen in all patients with EBV-infected NK-cell LPD, but not in any patients with EBV-infected T-cell LPD and were restored only after successful treatment.
  • The normal KIR repertoire is variable for each individual and it seems difficult to detect minimal residual EBV-infected lymphocytes.
  • However, the NK-cell repertoire is feasible for identifying EBV-infected NK-cell LPD and evaluating the treatment effect.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Epstein-Barr Virus Infections / immunology. Killer Cells, Natural / immunology. Killer Cells, Natural / virology. Lymphoproliferative Disorders / immunology. Stem Cell Transplantation
  • [MeSH-minor] Adolescent. Biomarkers / analysis. Biomarkers / metabolism. Child. Child, Preschool. Disease Progression. Drug Evaluation. Female. Humans. Infant. Male. Recurrence. Transplantation, Homologous. Treatment Outcome

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  • (PMID = 16823820.001).
  • [ISSN] 0361-8609
  • [Journal-full-title] American journal of hematology
  • [ISO-abbreviation] Am. J. Hematol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Biomarkers
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18. Crompton L, Khan N, Khanna R, Nayak L, Moss PA: CD4+ T cells specific for glycoprotein B from cytomegalovirus exhibit extreme conservation of T-cell receptor usage between different individuals. Blood; 2008 Feb 15;111(4):2053-61
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  • [Title] CD4+ T cells specific for glycoprotein B from cytomegalovirus exhibit extreme conservation of T-cell receptor usage between different individuals.
  • Antigen-specific CD8(+) cytotoxic T cells often demonstrate extreme conservation of T-cell receptor (TCR) usage between different individuals, but similar characteristics have not been documented for CD4(+) T cells.
  • CD4(+) T cells predominantly have a helper immune role, but a cytotoxic CD4(+) T-cell subset has been characterized, and we have studied the cytotoxic CD4(+) T-cell response to a peptide from human cytomegalovirus glycoprotein B presented through HLA-DRB*0701.
  • We show that this peptide elicits a cytotoxic CD4(+) T-cell response that averages 3.6% of the total CD4(+) T-cell repertoire of cytomegalovirus-seropositive donors.
  • Moreover, CD4(+) cytotoxic T-cell clones isolated from different individuals exhibit extensive conservation of TCR usage, which indicates strong T-cell clonal selection for peptide recognition.
  • Remarkably, this TCR sequence was recently reported in more than 50% of cases of CD4(+) T-cell large granular lymphocytosis.
  • Immunodominance of cytotoxic CD4(+) T cells thus parallels that of CD8(+) subsets and suggests that cytotoxic effector function is critical to the development of T-cell clonal selection, possibly from immune competition secondary to lysis of antigen-presenting cells.
  • In addition, these TCR sequences are highly homologous to those observed in HLA-DR7(+) patients with CD4(+) T-cell large granular lymphocytosis and implicate cytomegalovirus as a likely antigenic stimulus for this disorder.
  • [MeSH-major] CD4-Positive T-Lymphocytes / immunology. CD4-Positive T-Lymphocytes / virology. Cytomegalovirus Infections / immunology. Receptors, Antigen, T-Cell / immunology. Viral Envelope Proteins / immunology
  • [MeSH-minor] Cell Culture Techniques. Clone Cells. Dendritic Cells / immunology. Enzyme-Linked Immunosorbent Assay. Fetus. Fibroblasts / immunology. HLA-DR7 Antigen / immunology. Humans. RNA / genetics. RNA / isolation & purification. Skin / cytology. Skin / immunology

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  • (PMID = 17986665.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Grant] United Kingdom / Medical Research Council / / G9818340; United Kingdom / Medical Research Council / /
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / HLA-DR7 Antigen; 0 / Receptors, Antigen, T-Cell; 0 / Viral Envelope Proteins; 0 / glycoprotein B, Simplexvirus; 63231-63-0 / RNA
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19. Gogia A, Kakar A, Byotra SP, Bhargav M: Aggressive natural killer cell leukaemia: a rare and fatal disorder. J Assoc Physicians India; 2010 Nov;58:702-4
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  • [Title] Aggressive natural killer cell leukaemia: a rare and fatal disorder.
  • Natural killer (NK) cell neoplasms, which include extra-nodal NK/T-cell lymphoma (nasal and extra-nasal) and aggressive NK cell leukaemia, are generally rare, but they are more common in people of Oriental, Mexican and South American descent.
  • These neoplasms are highly aggressive, and show a strong association with Epstein-Barr virus.
  • Aggressive NK cell leukaemia affects younger patients, who present with poor general condition, fever, and disseminated disease; they often die within a short time from systemic disease or complications such as multi-organ failure.
  • Aggressive NK cell leukaemia must be distinguished from T-cell large granular lymphocyte leukaemia and indolent NK cell lympho-proliferative disorder, both of which are indolent.
  • We present a case of young Asian male with aggressive NK cell leukaemia who presented with a poor general condition and disseminated disease.
  • The patient had a rapidly progressive disease and died within weeks of diagnosis.
  • [MeSH-major] Killer Cells, Natural / pathology. Leukemia / pathology. Lymphoma / pathology

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  • (PMID = 21510468.001).
  • [ISSN] 0004-5772
  • [Journal-full-title] The Journal of the Association of Physicians of India
  • [ISO-abbreviation] J Assoc Physicians India
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] India
  • [Chemical-registry-number] 0 / Antibodies, Anti-Idiotypic; 0 / anti-IgG
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20. Kim D, Ko Y, Suh Y, Koo H, Huh J, Lee W: Characteristics of Epstein-Barr virus associated childhood non-Hodgkin's lymphoma in the Republic of Korea. Virchows Arch; 2005 Sep;447(3):593-6
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  • EBER-positive lymphomas account for 25% (20/80) and include NK/T-cell lymphoma (6/6), aggressive NK-cell leukemia (1/1), peripheral T cell lymphoma (5/11), diffuse large B-cell lymphoma (5/14), hydroa-like T-cell lymphoma (1/1), marginal zone B-cell lymphoma (1/2), and post-transplantation lymphoproliferative disorder (1/1).
  • Clinically, patients with EBV-positive B-cell lymphomas were cured with chemotherapy, whereas EBV-associated NK- and T cell lymphomas pursued fatal clinical course.
  • In conclusion, EBVs infected in childhood NHLs are frequently associated not only with NK- and T- cell lymphomas but also large B-cell lymphomas.

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  • (PMID = 15991005.001).
  • [ISSN] 0945-6317
  • [Journal-full-title] Virchows Archiv : an international journal of pathology
  • [ISO-abbreviation] Virchows Arch.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Germany
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21. Huh YO, Medeiros LJ, Ravandi F, Konoplev S, Jorgensen JL, Miranda RN: T-cell large granular lymphocyte leukemia associated with myelodysplastic syndrome: a clinicopathologic study of nine cases. Am J Clin Pathol; 2009 Mar;131(3):347-56
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  • [Title] T-cell large granular lymphocyte leukemia associated with myelodysplastic syndrome: a clinicopathologic study of nine cases.
  • We describe 9 patients with T-cell large granular lymphocyte leukemia (T-LGL) who also had a myelodysplastic syndrome (MDS).
  • The median absolute lymphocyte count was 1,300/microL (1.3 x 10(9)/L; range, 700-3,600/microL [0.7-3.6 x 10(9)/L]).
  • Immunophenotypic analysis showed a CD8+ T-cell population, and molecular analysis showed monoclonal T-cell receptor gene rearrangement in every case.
  • The MDS was classified as refractory cytopenia with multilineage dysplasia (RCMD, n = 5), refractory anemia (n = 2), RCMD with ringed sideroblasts (n = 1), and chronic myelomonocytic leukemia (n = 1).
  • We compared the data for these patients with T-LGL/MDS with a group that had only T-LGL.
  • The median hemoglobin level and absolute lymphocyte count were lower in patients with T-LGL/MDS (P < .05).
  • The frequency of coexistent T-LGL and MDS at our institution suggests an etiologic relationship rather than simple coincidence.
  • [MeSH-major] Leukemia, Large Granular Lymphocytic / complications. Leukemia, Large Granular Lymphocytic / genetics. Leukemia, Large Granular Lymphocytic / pathology. Myelodysplastic Syndromes / complications. Myelodysplastic Syndromes / genetics. Myelodysplastic Syndromes / pathology
  • [MeSH-minor] Adult. Aged. Blotting, Southern. Female. Flow Cytometry. Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor. Humans. Immunophenotyping. Lymphocyte Count. Male. Middle Aged. Polymerase Chain Reaction


22. Michalsen S, Schrumpf E, Beiske K, Tierens A, Stenberg V, Tjønnfjord GE: [Large granular lymphocytic leukaemia]. Tidsskr Nor Laegeforen; 2009 May 28;129(11):1098-102
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  • [Title] [Large granular lymphocytic leukaemia].
  • BACKGROUND: Large granular lymphocytic leukaemia (LGL-leukaemia) is considered a rare disease.
  • LGL-leukaemia is usually of the T-cell type, but a minority displays an NK-cell phenotype.
  • MATERIAL AND METHODS: We identified patients with LGL-leukaemia (with well-defined diagnostic criteria) diagnosed at Rikshospitalet University Hospital between 01.10.2001 and 31.12.2007.
  • RESULTS: LGL-leukaemia was diagnosed in 52 patients, 26 women and 26 men, median age of 59 (26 - 86) years, during the study period.
  • The leukaemia displayed NK-cell phenotype in one patient and T-cell phenotype in the remaining 51 patients.
  • Co-morbidity with autoimmune disease was common, and we also found a high prevalence of clonal B-cell disease (17 %).
  • INTERPRETATION: Our data support the notion that LGL-leukaemia is under-diagnosed.
  • Unexplained cytopenias should suggest the possibility of LGL-leukaemia, and appropriate diagnostic measures should be undertaken.
  • An early diagnosis may save patients an extensive and unnecessary diagnostic work-up and ensure that a simple and effective treatment is offered.
  • [MeSH-major] Leukemia, Large Granular Lymphocytic
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Bone Marrow Examination. Cyclosporine / therapeutic use. Early Diagnosis. Female. Humans. Immunosuppressive Agents / therapeutic use. Male. Middle Aged. Phenotype. Retrospective Studies

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  • [CommentIn] Tidsskr Nor Laegeforen. 2009 Aug 27;129(16):1660; author reply 1660 [19721490.001]
  • (PMID = 19488091.001).
  • [ISSN] 0807-7096
  • [Journal-full-title] Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række
  • [ISO-abbreviation] Tidsskr. Nor. Laegeforen.
  • [Language] nor
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] Norway
  • [Chemical-registry-number] 0 / Immunosuppressive Agents; 83HN0GTJ6D / Cyclosporine
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23. Sokol L, Loughran TP Jr: Large granular lymphocyte leukemia. Oncologist; 2006 Mar;11(3):263-73
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  • [Title] Large granular lymphocyte leukemia.
  • Clonal disorders of large granular lymphocytes (LGLs) represent a spectrum of biologically distinct lymphoproliferative diseases originating either from mature T cells (CD3+) or natural killer (NK) cells (CD3-).
  • Both subtypes, T-cell and NK-cell LGL leukemia, can manifest as indolent or aggressive disorders.
  • The majority of patients with T-cell LGL leukemia have a clinically indolent course with a median survival time >10 years.
  • Several cases of an aggressive variant (CD3+ CD56+) of T-cell LGL leukemia with a poor prognosis have also been reported.
  • Aggressive NK-cell LGL leukemia is usually a rapidly progressive disorder associated with Epstein-Barr virus (EBV), with a higher prevalence in Asia and South America.
  • This disease is usually refractory to conventional chemotherapy, with a median survival time of 2 months.
  • Chronic NK-cell leukemia/lymphocytosis is a rare EBV-negative disorder with an indolent clinical course.
  • The malignant origin of this subtype is uncertain because clonality is difficult to determine in LGLs of NK-cell origin.
  • [MeSH-major] Leukemia, T-Cell / diagnosis. Leukemia, T-Cell / therapy
  • [MeSH-minor] Algorithms. Autoimmune Diseases / etiology. Cytogenetic Analysis. Diagnosis, Differential. Hematologic Diseases / etiology. Humans. Phenotype

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  • (PMID = 16549811.001).
  • [ISSN] 1083-7159
  • [Journal-full-title] The oncologist
  • [ISO-abbreviation] Oncologist
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Number-of-references] 76
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24. Xu X, Broome EH, Rashidi HH, South ST, Dell'aquila ML, Wang HY: CD20dim-positive T-cell large granular lymphocytic leukemia in a patient with concurrent hairy cell leukemia and plasma cell myeloma. Int J Clin Exp Pathol; 2010;3(8):798-807
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  • [Title] CD20dim-positive T-cell large granular lymphocytic leukemia in a patient with concurrent hairy cell leukemia and plasma cell myeloma.
  • We report a CD20dim- positive T-cell large granular lymphocytic (T-LGL) leukemia in a patient with concurrent hairy cell leukemia and plasma cell myeloma.
  • This patient was first diagnosed with T-LGL leukemia with dim CD20 expression, which by itself was a rare entity.
  • He received no treatment for T-LGL leukemia.
  • The patient later developed a hairy cell leukemia, which went into complete clinical remission after one cycle of 2-CdA.
  • Five years later, he was diagnosed with a third malignancy, plasma cell myeloma.
  • Complex cytogenetic aberrancies were present at the time when plasma cell myeloma was diagnosed.
  • [MeSH-major] Antigens, CD20 / metabolism. Leukemia, Hairy Cell / pathology. Leukemia, Large Granular Lymphocytic / metabolism. Leukemia, Large Granular Lymphocytic / pathology. Multiple Myeloma / pathology. Neoplasms, Multiple Primary / pathology

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  • (PMID = 21151394.001).
  • [ISSN] 1936-2625
  • [Journal-full-title] International journal of clinical and experimental pathology
  • [ISO-abbreviation] Int J Clin Exp Pathol
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal, Murine-Derived; 0 / Antigens, CD20; 0 / Antineoplastic Agents; 4F4X42SYQ6 / Rituximab
  • [Other-IDs] NLM/ PMC2993231
  • [Keywords] NOTNLM ; CD20 / T-cell large granular lymphocytic leukemia / hairy cell leukemia / plasma cell myeloma
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25. Kim DH, Kamel-Reid S, Chang H, Sutherland R, Jung CW, Kim HJ, Lee JJ, Lipton JH: Natural killer or natural killer/T cell lineage large granular lymphocytosis associated with dasatinib therapy for Philadelphia chromosome positive leukemia. Haematologica; 2009 Jan;94(1):135-9
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  • [Title] Natural killer or natural killer/T cell lineage large granular lymphocytosis associated with dasatinib therapy for Philadelphia chromosome positive leukemia.
  • Dasatinib, a dual tyrosine kinase inhibitor, is known to modulate or suppress T-cell activation and proliferation.
  • We report a series of 8 patients who developed chronic peripheral lymphocytosis, identified as natural killer cells or natural killer/T-cells based on their large granular lymphocyte morphologies and CD16(+), CD56(+), CD3(-) or CD3(+) immunophenotypic profiles, out of 18 patients receiving dasatinib therapy.
  • All cases that developed large granular lymphocyte lymphocytosis achieved optimal molecular response (8/8 in large granular lymphocyte(+) patients vs. 3/10 in large granular lymphocyte(-) patients, p=0.002).
  • A (51)Cr release assay demonstrated that natural killer cell cytotoxicity has been enhanced in a case of large granular lymphocyte lymphocytosis compared to normal healthy donors, and that natural killer cell cytotoxicity in dasatinib-responders was superior to that in non-responders.
  • In summary, the present study suggests that natural killer or natural killer/T cell lineage large granular lymphocyte lymphocytosis develops in association with dasatinib therapy and that large granular lymphocyte might have a therapeutic effect on Ph(+) leukemic cells.
  • [MeSH-major] Antineoplastic Agents / adverse effects. Cell Lineage / drug effects. Killer Cells, Natural / drug effects. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy. Lymphocytosis / chemically induced. Natural Killer T-Cells / drug effects. Pyrimidines / adverse effects. Thiazoles / adverse effects

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  • (PMID = 19066329.001).
  • [ISSN] 1592-8721
  • [Journal-full-title] Haematologica
  • [ISO-abbreviation] Haematologica
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Italy
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Pyrimidines; 0 / Thiazoles; RBZ1571X5H / Dasatinib
  • [Other-IDs] NLM/ PMC2625403
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26. Baesso I, Pavan L, Boscaro E, Miorin M, Facco M, Trentin L, Agostini C, Zambello R, Semenzato G: T-cell type lymphoproliferative disease of granular lymphocytes (LDGL) is equipped with a phenotypic pattern typical of effector cytotoxic cells. Leuk Res; 2007 Mar;31(3):371-7
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  • [Title] T-cell type lymphoproliferative disease of granular lymphocytes (LDGL) is equipped with a phenotypic pattern typical of effector cytotoxic cells.
  • By analyzing the expression of several cytotoxic markers, killer-immunoglobulin-like receptors (KIRs), CD94/CD159, CD314 and natural cytotoxicity receptors (NCRs), in 22 CD3+ lymphoproliferative disease of granular lymphocyte (LDGL) patients we investigated whether granular lymphocytes (GLs) displayed the phenotype of fully differentiated cytotoxic cells.
  • In conclusion, GLs in CD3+ LDGL patients typically show the phenotype of fully differentiated CTL, whereas the expression of NK receptors does not represent a common feature of the proliferating clone.
  • [MeSH-major] Lymphocytes / immunology. Lymphoproliferative Disorders / immunology. T-Lymphocytes, Cytotoxic / immunology
  • [MeSH-minor] Aged. Antigens, CD3 / immunology. Cell Differentiation / immunology. Female. Humans. Immunophenotyping. Male. NK Cell Lectin-Like Receptor Subfamily K. Receptors, IgG / immunology. Receptors, Immunologic / biosynthesis. Receptors, Immunologic / immunology. Receptors, KIR. Receptors, Natural Killer Cell

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  • (PMID = 16982092.001).
  • [ISSN] 0145-2126
  • [Journal-full-title] Leukemia research
  • [ISO-abbreviation] Leuk. Res.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antigens, CD3; 0 / KLRK1 protein, human; 0 / NK Cell Lectin-Like Receptor Subfamily K; 0 / Receptors, IgG; 0 / Receptors, Immunologic; 0 / Receptors, KIR; 0 / Receptors, Natural Killer Cell
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27. Olteanu H, Karandikar NJ, Eshoa C, Kroft SH: Laboratory findings in CD4(+) large granular lymphocytoses. Int J Lab Hematol; 2010 Feb;32(1 Pt 1):e9-16
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  • [Title] Laboratory findings in CD4(+) large granular lymphocytoses.
  • Large granular lymphocytic (LGL) leukemia is an uncommon disorder of mature T or natural killer (NK) cells.
  • Most T-LGL proliferations are CD3(+)/CD8(+), although rare CD4(+) clonal T-LGL expansions have been reported.
  • We report the clinicopathologic features of eight patients with aberrant CD4(+), cytotoxic T-cell lymphocytoses.
  • Morphologic expansions of granulated lymphocytes were evident in 6/8.
  • Abnormal levels of expression of two or more T-cell antigens were seen in all cases.
  • Our results support that CD4(+) T-LGL lymphocytosis is a clonal disorder with clinicopathologic characteristics distinct from the more common CD8(+) variant.
  • [MeSH-major] CD4-Positive T-Lymphocytes / immunology. Leukemia, Large Granular Lymphocytic / immunology

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  • (PMID = 20089001.001).
  • [ISSN] 1751-553X
  • [Journal-full-title] International journal of laboratory hematology
  • [ISO-abbreviation] Int J Lab Hematol
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antigens, CD56; 0 / Antigens, CD57
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28. Wilentz SE: Blastic natural killer-cell lymphoma: a case report. Cutis; 2006 Jan;77(1):42-4
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  • [Title] Blastic natural killer-cell lymphoma: a case report.
  • This article presents a case of blastic natural killer (NK)-cell lymphoma.
  • Most cases, including the one presented here, follow an aggressive clinical course.
  • [MeSH-major] Killer Cells, Natural / pathology. Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology

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  • (PMID = 16475495.001).
  • [ISSN] 0011-4162
  • [Journal-full-title] Cutis
  • [ISO-abbreviation] Cutis
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antigens, CD; 0 / Antigens, Neoplasm; 0 / Biomarkers, Tumor
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29. Brodtman DH, Rosenthal DW, Redner A, Lanzkowsky P, Bonagura VR: Immunodeficiency in children with acute lymphoblastic leukemia after completion of modern aggressive chemotherapeutic regimens. J Pediatr; 2005 May;146(5):654-61
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  • [Title] Immunodeficiency in children with acute lymphoblastic leukemia after completion of modern aggressive chemotherapeutic regimens.
  • OBJECTIVE: To determine the prevalence, duration, and a potential cause of humoral defect(s) in children with acute lymphoblastic leukemia (ALL) at least 1 year after completion of chemotherapy.
  • T-, B-, and NK-cell numbers and proliferative responses to mitogens were all normal.
  • [MeSH-major] Antibody Formation / drug effects. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Asparaginase / therapeutic use. Communicable Diseases / immunology. Daunorubicin / therapeutic use. Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy. Prednisone / therapeutic use. Vincristine / therapeutic use

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  • (PMID = 15870670.001).
  • [ISSN] 0022-3476
  • [Journal-full-title] The Journal of pediatrics
  • [ISO-abbreviation] J. Pediatr.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 5J49Q6B70F / Vincristine; EC 3.5.1.1 / Asparaginase; VB0R961HZT / Prednisone; ZS7284E0ZP / Daunorubicin; PVDA protocol
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30. Zhang R, Shah MV, Yang J, Nyland SB, Liu X, Yun JK, Albert R, Loughran TP Jr: Network model of survival signaling in large granular lymphocyte leukemia. Proc Natl Acad Sci U S A; 2008 Oct 21;105(42):16308-13
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  • [Title] Network model of survival signaling in large granular lymphocyte leukemia.
  • T cell large granular lymphocyte (T-LGL) leukemia features a clonal expansion of antigen-primed, competent, cytotoxic T lymphocytes (CTL).
  • To systematically understand signaling components that determine the survival of CTL in T-LGL leukemia, we constructed a T-LGL survival signaling network by integrating the signaling pathways involved in normal CTL activation and the known deregulations of survival signaling in leukemic T-LGL.
  • Our model suggests that the persistence of IL-15 and PDGF is sufficient to reproduce all known deregulations in leukemic T-LGL.
  • This finding leads to the following predictions: (i) Inhibiting PDGF signaling induces apoptosis in leukemic T-LGL. (ii) Sphingosine kinase 1 and NFkappaB are essential for the long-term survival of CTL in T-LGL leukemia. (iii) NFkappaB functions downstream of PI3K and prevents apoptosis through maintaining the expression of myeloid cell leukemia sequence 1. (iv) T box expressed in T cells (T-bet) should be constitutively activated concurrently with NFkappaB activation to reproduce the leukemic T-LGL phenotype.
  • The model will be useful in identifying potential therapeutic targets for T-LGL leukemia and generating long-term competent CTL necessary for tumor and cancer vaccine development.

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  • (PMID = 18852469.001).
  • [ISSN] 1091-6490
  • [Journal-full-title] Proceedings of the National Academy of Sciences of the United States of America
  • [ISO-abbreviation] Proc. Natl. Acad. Sci. U.S.A.
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / R01 CA098472; United States / NCI NIH HHS / CA / R01 CA 94872
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Adaptor Proteins, Signal Transducing; 0 / Interleukin-15; 0 / NF-kappa B; 0 / Platelet-Derived Growth Factor; 0 / SKIP protein, human; 0 / STAT3 Transcription Factor
  • [Other-IDs] NLM/ PMC2571012
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31. Mohan SR, Maciejewski JP: Diagnosis and therapy of neutropenia in large granular lymphocyte leukemia. Curr Opin Hematol; 2009 Jan;16(1):27-34
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  • [Title] Diagnosis and therapy of neutropenia in large granular lymphocyte leukemia.
  • PURPOSE OF REVIEW: T-cell large granular lymphocyte leukemia is a chronic clonal lymphoproliferation of cytotoxic T cells often associated with immune-mediated cytopenias.
  • This review will address the diagnostic challenges of and therapeutic options for T-cell large granular lymphocyte leukemia.
  • SUMMARY: T-cell large granular lymphocyte leukemia may assume an indolent course but sometimes manifests with significant cytopenias.
  • In these cases, a variety of agents maybe used successfully though chronic therapy is often necessary.
  • [MeSH-major] Leukemia, Large Granular Lymphocytic / complications. Leukemia, Large Granular Lymphocytic / therapy. Neutropenia / therapy

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  • (PMID = 19057202.001).
  • [ISSN] 1531-7048
  • [Journal-full-title] Current opinion in hematology
  • [ISO-abbreviation] Curr. Opin. Hematol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Number-of-references] 89
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32. Bareau B, Rey J, Hamidou M, Donadieu J, Morcet J, Reman O, Schleinitz N, Tournilhac O, Roussel M, Fest T, Lamy T: Analysis of a French cohort of patients with large granular lymphocyte leukemia: a report on 229 cases. Haematologica; 2010 Sep;95(9):1534-41
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  • [Title] Analysis of a French cohort of patients with large granular lymphocyte leukemia: a report on 229 cases.
  • BACKGROUND: Large granular lymphocyte leukemia is a rare lymphoproliferative disorder associated with autoimmune diseases and impaired hematopoiesis.
  • This study describes the clinical and biological characteristics of 229 patients with T-cell or NK-cell large granular lymphocyte leukemia.
  • DESIGN AND METHODS: The diagnosis was based on a large granular lymphocyte expansion (> 0.5x10(9)/L) lasting more than 6 months.
  • Monoclonal T-cell receptor gamma gene rearrangement was detected in all the cases of T-cell large granular lymphocyte leukemia.
  • Patients with chronic NK-cell lymphocytosis had an indolent disease, while those with multiorgan large granular lymphocyte infiltration and an aggressive clinical disease were considered to have NK-cell large granular lymphocyte leukemia.
  • RESULTS: The diagnosis of T-cell large granular lymphocyte leukemia was confirmed in 201 cases, chronic NK-cell lymphocytosis in 27 cases and NK-cell large granular lymphocyte leukemia in one case.
  • There were 15 large granular lymphocyte leukemia-related deaths.
  • CONCLUSIONS: Patients with T-cell large granular lymphocyte leukemia and chronic NK-cell lymphocytosis have similar clinical and biological features and responses to treatment.
  • [MeSH-major] Killer Cells, Natural / pathology. Leukemia, Large Granular Lymphocytic / diagnosis. Leukemia, Large Granular Lymphocytic / epidemiology. T-Lymphocytes / pathology
  • [MeSH-minor] Adult. Aged. Cohort Studies. Female. France / epidemiology. Humans. Lymphocytosis / diagnosis. Male. Middle Aged. Registries. Treatment Outcome

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  • (PMID = 20378561.001).
  • [ISSN] 1592-8721
  • [Journal-full-title] Haematologica
  • [ISO-abbreviation] Haematologica
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Italy
  • [Other-IDs] NLM/ PMC2930955
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33. Muñoz L, Lasa A, Carricondo MT, Hernández C, Ubeda J, Nomdedéu JF: Comparative analysis of ZAP-70 expression and Ig VH mutational status in B-cell chronic lymphocytic leukemia. Cytometry B Clin Cytom; 2007 Mar;72(2):96-102
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  • [Title] Comparative analysis of ZAP-70 expression and Ig VH mutational status in B-cell chronic lymphocytic leukemia.
  • BACKGROUND: B-cell chronic lymphocytic leukemia (CLL) is a heterogeneous disorder with respect to its clinical course.
  • Accurate identification of prognostic factors is becoming increasingly important in order to determine those patients requiring aggressive treatments.
  • Positivity was established using two methods: comparing ZAP70 expression in B-cells with T-cells using cytoplasmic CD3 (ZAP-70/T) and with NK-cell reactivity (ZAP-70/NK).
  • RESULTS: Using a T-cell marker, 58% of patients were ZAP-70+ and 42% were ZAP-70-.
  • NK-cell comparisons gave only 6% of ZAP-70 positivity in B-CLL, and in six cases the absence of a clearly defined NK-cell population precluded the ZAP70 analysis.
  • CONCLUSIONS: ZAP-70 reactivity using a T-cell marker as a control allows to identify the majority of patients with an unmutated Ig VH genotype.
  • [MeSH-major] Immunoglobulin Heavy Chains / genetics. Immunoglobulin Variable Region / genetics. Leukemia, Lymphocytic, Chronic, B-Cell / blood. Leukemia, Lymphocytic, Chronic, B-Cell / genetics. ZAP-70 Protein-Tyrosine Kinase / blood
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Antibodies, Monoclonal / immunology. Base Sequence. Female. Humans. Killer Cells, Natural / metabolism. Male. Middle Aged. Molecular Sequence Data. Mutation. Sequence Homology, Nucleic Acid. T-Lymphocytes / metabolism. Tumor Cells, Cultured

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  • [Copyright] (c) 2006 International Society for Analytical Cytology.
  • [CommentIn] Cytometry B Clin Cytom. 2007 Mar;72(2):94-5 [17285625.001]
  • (PMID = 17051526.001).
  • [ISSN] 1552-4949
  • [Journal-full-title] Cytometry. Part B, Clinical cytometry
  • [ISO-abbreviation] Cytometry B Clin Cytom
  • [Language] eng
  • [Publication-type] Evaluation Studies; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Immunoglobulin Heavy Chains; 0 / Immunoglobulin Variable Region; EC 2.7.10.2 / ZAP-70 Protein-Tyrosine Kinase
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34. Risitano AM, Maciejewski JP, Selleri C, Rotoli B: Function and malfunction of hematopoietic stem cells in primary bone marrow failure syndromes. Curr Stem Cell Res Ther; 2007 Jan;2(1):39-52
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  • Primary bone marrow failure syndromes are a heterogeneous group of diseases with specific pathogenic mechanisms, which share a profound impairment of the hematopoietic stem cell pool resulting in global or selective marrow aplasia.
  • In idiopathic Aplastic Anemia (AA) immunological mechanisms play a pivotal role in damaging the hematopoietic compartment, resulting in a depletion of the hematopoietic stem cell pool.
  • Clinical and experimental evidences support the presence of a T cell-mediated immune attack, as confirmed by clonally expanded lymphocytes, even if the target antigens are still undefined.
  • Other recent data suggest that similar antigen-driven immune mechanisms may be involved in marrow failure associated with lymphoproliferative or autoimmune disorders characterized by clonal expansion of T lymphocytes, such as Large Granular Lymphocyte leukemia.
  • The study of hematopoietic stem cell function in marrow failure syndromes provides hints for specific molecular pathways disturbed in many diseases of hematopoietic and non-hematopoietic stem cells.
  • Beyond the specific interest of investigators involved in the field of these rare diseases, marrow failure syndromes represent a model that provides intriguing insight into quantity and function of normal hematopoietic stem cells, improving our knowledge on stem cell biology.
  • [MeSH-minor] Anemia, Aplastic / pathology. Animals. Hemoglobinuria, Paroxysmal / pathology. Humans. Leukemia, Large Granular Lymphocytic / pathology. Syndrome

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  • (PMID = 18220891.001).
  • [ISSN] 1574-888X
  • [Journal-full-title] Current stem cell research & therapy
  • [ISO-abbreviation] Curr Stem Cell Res Ther
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United Arab Emirates
  • [Number-of-references] 146
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35. Risitano AM, Maciejewski JP, Muranski P, Wlodarski M, O'Keefe C, Sloand EM, Young NS: Large granular lymphocyte (LGL)-like clonal expansions in paroxysmal nocturnal hemoglobinuria (PNH) patients. Leukemia; 2005 Feb;19(2):217-22
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  • [Title] Large granular lymphocyte (LGL)-like clonal expansions in paroxysmal nocturnal hemoglobinuria (PNH) patients.
  • In vivo expansion of dominant T-cell clones can reflect an antigen-driven immune response but may also represent autonomous proliferation, such as in large granular lymphocytic (LGL)-leukemia.
  • T-cell clonality can be assessed by a combination of T-cell receptor (TCR) flow cytometry and complementarity-determining-region-3 (CDR3) molecular analysis.
  • We studied 24 PNH patients for evidence of in vivo dominant T-cell responses by flow cytometry; TCR-Vbeta-specific expansions were identified in all patients.
  • In four cases, extreme expansions of one Vbeta-subset of CD8+/CD28-/CD56+ (effector) phenotype mimicked subclinical LGL-disease.
  • We conclude that the molecular analysis of TCR-beta chain may demonstrate clonal LGL-like expansions at unexpected frequency in PNH patients.
  • Our observations blur the classical boundaries between different bone marrow failure syndromes such as AA, PNH, and LGL, and support the hypothesis that in PNH, the mutant clone may expand as a result of an immune-escape from antigen-driven lymphocyte attack on hematopoietic progenitors.
  • [MeSH-major] Leukemia, Lymphoid / etiology. Membrane Proteins / blood


36. Suzuki R, Suzumiya J, Nakamura S, Kagami Y, Kameoka JI, Sakai C, Mukai H, Takenaka K, Yoshino T, Tsuzuki T, Sugimori H, Kawa K, Kodera Y, Oshimi K, NK-cell Tumor Study Group: Hematopoietic stem cell transplantation for natural killer-cell lineage neoplasms. Bone Marrow Transplant; 2006 Feb;37(4):425-31
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  • [Title] Hematopoietic stem cell transplantation for natural killer-cell lineage neoplasms.
  • Neoplasms of natural killer (NK)-lineage are rare.
  • Their prognosis is generally poor except for cases of solitary nasal NK-cell lymphoma.
  • The NK-cell Tumor Study Group performed a survey in Japan on patients diagnosed between 1994 and 1998.
  • The underlying diseases were myeloid/NK cell precursor acute leukemia (n = 4), blastic NK-cell lymphoma (n = 11), aggressive NK-cell leukemia (n = 3), and nasal-type extranodal NK-cell lymphoma (n = 22).
  • Sixteen died of disease progression, and six of treatment-related causes.
  • These findings suggest that the HSCT is a promising treatment strategy for NK-cell lineage.
  • [MeSH-major] Hematopoietic Stem Cell Transplantation. Killer Cells, Natural / pathology. Leukemia / therapy. Lymphoma / therapy
  • [MeSH-minor] Adolescent. Adult. Aged. Aged, 80 and over. Child. Child, Preschool. Disease Progression. Female. Follow-Up Studies. Humans. Infant. Infant, Newborn. Japan. Male. Middle Aged. Prognosis. Survival Rate. Transplantation Conditioning. Transplantation, Autologous. Transplantation, Homologous


37. Ishmael J, Dugard PH: A review of perchloroethylene and rat mononuclear cell leukemia. Regul Toxicol Pharmacol; 2006 Jul;45(2):178-84
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  • [Title] A review of perchloroethylene and rat mononuclear cell leukemia.
  • Mononuclear cell leukemia (MNCL) is an extremely common spontaneous disease of ageing F344 rats accompanied by splenomegaly, anemia, thrombocytopenia, and leukemic infiltration (initially of the spleen, liver, and lung).
  • MNCL cells possess natural killer (NK) cell characteristics and apparently, the neoplastic cells derive from large granular lymphocytes (LGL), hence the alternative name of LGL leukemia.
  • LGL leukemia is uncommon in man and occurs in two forms: T-LGL leukemia which has a chronic course, and the much rarer NK-LGL leukemia.
  • In addition to cell type, the latter resembles F344 LGL leukemia being acute in course and involving more pronounced splenomegaly and thrombocytopenia.
  • Chemically related increases in MNCL in F344 rats have not been associated with induction of human LGL leukemia.
  • [MeSH-major] Carcinogens, Environmental / toxicity. Leukemia, Lymphoid / chemically induced. Tetrachloroethylene / toxicity

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  • (PMID = 16684583.001).
  • [ISSN] 0273-2300
  • [Journal-full-title] Regulatory toxicology and pharmacology : RTP
  • [ISO-abbreviation] Regul. Toxicol. Pharmacol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Carcinogens, Environmental; TJ904HH8SN / Tetrachloroethylene
  • [Number-of-references] 53
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38. Bertilaccio MT, Scielzo C, Simonetti G, Ponzoni M, Apollonio B, Fazi C, Scarfò L, Rocchi M, Muzio M, Caligaris-Cappio F, Ghia P: A novel Rag2-/-gammac-/--xenograft model of human CLL. Blood; 2010 Feb 25;115(8):1605-9
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  • Easily reproducible animal models that allow for study of the biology of chronic lymphocytic leukemia (CLL) and to test new therapeutic agents have been very difficult to establish.
  • We have developed a novel transplantable xenograft murine model of CLL by engrafting the CLL cell line MEC1 into Rag2(-/-)gamma(c)(-/-) mice.
  • These mice lack B, T, and natural killer (NK) cells, and, in contrast to nude mice that retain NK cells, appear to be optimal recipient for MEC1 cells, which were successfully transplanted through either subcutaneous or intravenous routes.
  • This model closely resembles aggressive human CLL and could be very useful for evaluating both the biologic basis of CLL growth and dissemination as well as the efficacy of new therapeutic agents.
  • [MeSH-major] DNA-Binding Proteins. Disease Models, Animal. Leukemia, Lymphocytic, Chronic, B-Cell
  • [MeSH-minor] Animals. Cell Line, Tumor. Humans. Mice. Mice, Inbred BALB C. Mice, Knockout. Neoplasm Transplantation. Transplantation, Heterologous

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  • (PMID = 20018917.001).
  • [ISSN] 1528-0020
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / DNA-Binding Proteins; 0 / Rag2 protein, mouse
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39. Stamatopoulos K, Economidou D, Papadaki T, Vadikolia C, Papathanasiou M, Memmos D, Fassas A: Large granular lymphocyte leukemia after renal transplantation: an immunologic, immunohistochemical, and genotypic study. Transplantation; 2007 Jan 15;83(1):102-3
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  • [Title] Large granular lymphocyte leukemia after renal transplantation: an immunologic, immunohistochemical, and genotypic study.
  • [MeSH-major] Kidney Failure, Chronic / surgery. Kidney Transplantation / adverse effects. Leukemia, Lymphoid / immunology. Living Donors
  • [MeSH-minor] Antigens, CD / blood. CD4-Positive T-Lymphocytes / microbiology. Humans. Male. Middle Aged. Postoperative Complications / immunology. Postoperative Complications / pathology. T-Lymphocytes / immunology


40. Ko YH, Park S, Kim K, Kim SJ, Kim WS: Aggressive natural killer cell leukemia: is Epstein-Barr virus negativity an indicator of a favorable prognosis? Acta Haematol; 2008;120(4):199-206
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  • [Title] Aggressive natural killer cell leukemia: is Epstein-Barr virus negativity an indicator of a favorable prognosis?
  • Aggressive natural killer (NK) cell leukemia (ANKL) is a prototype of an Epstein-Barr virus (EBV)-associated lymphoid malignancy, which is characterized by a fulminant clinical course and a median survival interval <2 months.
  • In conclusion, EBV-negative ANKL is an uncommon malignancy that pursues a less aggressive clinical course than EBV-positive ANKL.
  • [MeSH-major] Epstein-Barr Virus Infections / virology. Leukemia, T-Cell / virology
  • [MeSH-minor] Adolescent. Adult. Aged. Fatal Outcome. Female. Humans. Kaplan-Meier Estimate. Killer Cells, Natural / immunology. Male. Middle Aged. Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology. Recurrence. Young Adult

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  • [Copyright] Copyright 2009 S. Karger AG, Basel.
  • (PMID = 19153474.001).
  • [ISSN] 1421-9662
  • [Journal-full-title] Acta haematologica
  • [ISO-abbreviation] Acta Haematol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Switzerland
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41. Kusumoto S, Mori S, Nosaka K, Morita-Hoshi Y, Onishi Y, Kim SW, Watanabe T, Heike Y, Tanosaki R, Takaue Y, Tobinai K: T-cell large granular lymphocyte leukemia of donor origin after cord blood transplantation. Clin Lymphoma Myeloma; 2007 Jul;7(7):475-9
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  • [Title] T-cell large granular lymphocyte leukemia of donor origin after cord blood transplantation.
  • We report the first case of T-cell large granular lymphocyte leukemia of donor origin after a second cord blood transplantation for acute myeloid leukemia, and review the literature regarding rare cases of T-cell-origin posttransplantation lymphoproliferative disorders.
  • [MeSH-major] Blood Donors. Cord Blood Stem Cell Transplantation. Leukemia, Myeloid, Acute / therapy. Leukemia, T-Cell / etiology. Neoplasms, Second Primary / etiology


42. Yoo EH, Kim HJ, Lee ST, Kim WS, Kim SH: Frequent CD7 antigen loss in aggressive natural killer-cell leukemia: a useful diagnostic marker. Korean J Lab Med; 2009 Dec;29(6):491-6
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  • [Title] Frequent CD7 antigen loss in aggressive natural killer-cell leukemia: a useful diagnostic marker.
  • BACKGROUND: Aggressive natural killer-cell leukemia (ANKL) is a rare neoplasm characterized by systemic proliferation of NK cells.
  • However, the differential diagnosis of NK lymphoproliferative disorders is difficult because of the absence of a distinct diagnostic hallmark.
  • The immunophenotype of the leukemic NK-cells was cytoplasmic CD3(+), surface CD3(-), CD16/56(+), CD2(+), and CD5(-).
  • In conjunction with the cytogenetic findings, this characteristic immunophenotypic finding can serve as a reliable marker for the timely diagnosis of ANKL.
  • Therefore, immunophenotypic analysis of CD7 expression should be included in the diagnosis of NK cell neoplasms.
  • [MeSH-major] Antigens, CD7 / analysis. Biomarkers, Tumor / analysis. Leukemia, Large Granular Lymphocytic / diagnosis
  • [MeSH-minor] Adolescent. Adult. Aged. Blood Cell Count. Child. Child, Preschool. Cytogenetics. Female. Herpesvirus 4, Human / isolation & purification. Humans. Immunophenotyping. Karyotyping. Male. Middle Aged. Retrospective Studies

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  • (PMID = 20046078.001).
  • [ISSN] 1598-6535
  • [Journal-full-title] The Korean journal of laboratory medicine
  • [ISO-abbreviation] Korean J Lab Med
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Korea (South)
  • [Chemical-registry-number] 0 / Antigens, CD7; 0 / Biomarkers, Tumor
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43. Jaccard A, Petit B, Girault S, Suarez F, Gressin R, Zini JM, Coiteux V, Larroche C, Devidas A, Thiéblemont C, Gaulard P, Marin B, Gachard N, Bordessoule D, Hermine O: L-asparaginase-based treatment of 15 western patients with extranodal NK/T-cell lymphoma and leukemia and a review of the literature. Ann Oncol; 2009 Jan;20(1):110-6
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  • [Title] L-asparaginase-based treatment of 15 western patients with extranodal NK/T-cell lymphoma and leukemia and a review of the literature.
  • BACKGROUND: Extranodal natural killer (NK)/T-cell lymphoma, nasal type, and aggressive NK-cell leukemia are highly aggressive diseases with a poor outcome.
  • PATIENTS AND METHODS: We report a multicentric French retrospective study of 15 patients with relapsed, refractory, or disseminated disease, treated with L-asparaginase-containing regimens in seven French centers.
  • CONCLUSION: These data, although retrospective, confirm the excellent activity of L-asparaginase-containing regimens in refractory extranodal NK/T-cell lymphoma and aggressive NK-cell leukemia.
  • Therefore, L-asparaginase-based regimen should be considered as a salvage treatment, especially for patients with disseminated disease.
  • First-line L-asparaginase combination therapy for extranodal NK/T-cell lymphoma and aggressive NK-cell leukemia should be tested in prospective trials.

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  • (PMID = 18701429.001).
  • [ISSN] 1569-8041
  • [Journal-full-title] Annals of oncology : official journal of the European Society for Medical Oncology
  • [ISO-abbreviation] Ann. Oncol.
  • [Language] ENG
  • [Publication-type] Evaluation Studies; Journal Article; Multicenter Study; Review
  • [Publication-country] England
  • [Chemical-registry-number] EC 3.5.1.1 / Asparaginase
  • [Number-of-references] 26
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44. Makishima H, Ito T, Momose K, Nakazawa H, Shimodaira S, Kamijo Y, Nakazawa Y, Ichikawa N, Ueno M, Kobayashi H, Kitano K, Saito H, Kiyosawa K, Ishida F: Chemokine system and tissue infiltration in aggressive NK-cell leukemia. Leuk Res; 2007 Sep;31(9):1237-45
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  • [Title] Chemokine system and tissue infiltration in aggressive NK-cell leukemia.
  • NK cell-type lymphoproliferative disease of granular lymphocytes can be subdivided into aggressive NK-cell leukemia (ANKL) and chronic NK-cell lymphocytosis (CNKL).
  • [MeSH-major] Chemokines / blood. Fas Ligand Protein / metabolism. Killer Cells, Natural / pathology. Leukemia, Lymphoid / blood. Lymphocytosis / blood

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  • (PMID = 17123604.001).
  • [ISSN] 0145-2126
  • [Journal-full-title] Leukemia research
  • [ISO-abbreviation] Leuk. Res.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Chemokines; 0 / Fas Ligand Protein; 0 / RNA, Messenger; 0 / RNA, Neoplasm
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45. Monjanel H, Hourioux C, Arbion F, Colombat P, Lissandre S, Regner MP, Senecal D: Rapid and durable molecular response of refractory T-cell large granular lymphocyte leukemia after alemtuzumab treatment. Leuk Res; 2010 Aug;34(8):e197-9
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  • [Title] Rapid and durable molecular response of refractory T-cell large granular lymphocyte leukemia after alemtuzumab treatment.
  • [MeSH-major] Antibodies, Monoclonal / therapeutic use. Antibodies, Neoplasm / therapeutic use. Antineoplastic Agents / therapeutic use. Drug Resistance, Neoplasm. Leukemia, Large Granular Lymphocytic / drug therapy. Salvage Therapy

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  • (PMID = 20211489.001).
  • [ISSN] 1873-5835
  • [Journal-full-title] Leukemia research
  • [ISO-abbreviation] Leuk. Res.
  • [Language] eng
  • [Publication-type] Case Reports; Letter
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / Antibodies, Neoplasm; 0 / Antineoplastic Agents; 3A189DH42V / alemtuzumab
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46. Cabrera ME, Eizuru Y, Itoh T, Koriyama C, Tashiro Y, Ding S, Rey S, Akiba S, Corvalan A: Nasal natural killer/T-cell lymphoma and its association with type "i"/XhoI loss strain Epstein-Barr virus in Chile. J Clin Pathol; 2007 Jun;60(6):656-60
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  • [Title] Nasal natural killer/T-cell lymphoma and its association with type "i"/XhoI loss strain Epstein-Barr virus in Chile.
  • BACKGROUND: Nasal T/natural killer (NK)-cell lymphoma is an aggressive type of non-Hodking's lymphoma associated with Epstein-Barr virus (EBV) and striking geographical variations worldwide.
  • AIM: To characterise nasal NK/T-cell lymphoma associated with genotypes of EBV in Chile, a Latin American country, where multiple strains of EBV, including two new recombinant strains, in healthy individuals were recently found.
  • METHODS: Cases with diagnosis of primary nasal lymphoma were selected for histological and immunohistochemical analysis (CD3, CD3e, CD4, CD8, CD79a, CD56, CD57 and TIA-1) and in-situ hybridisation, serology and genotyping analysis for EBV.
  • RESULTS: Out of 22 cases, 9 (41%) cases fulfilled the World Health Organization criteria for nasal NK/T-cell lymphoma; of these 7 (78%) cases were positive for EBV.
  • CONCLUSION: Although nasal NK/T-cell lymphomas from Chile share similar clinicopathological features, high association with EBV and unfavourable prognosis with those described elsewhere, genotype analysis shows that the new recombinant type "i"/XhoI loss strain might contribute to explain the intermediate incidence of nasal NK/T-cell lymphomas in Latin America.
  • [MeSH-major] Epstein-Barr Virus Infections / complications. Herpesvirus 4, Human / genetics. Killer Cells, Natural / pathology. Lymphoma, T-Cell / virology. Nose Neoplasms / virology

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  • (PMID = 16775124.001).
  • [ISSN] 0021-9746
  • [Journal-full-title] Journal of clinical pathology
  • [ISO-abbreviation] J. Clin. Pathol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / RNA, Viral
  • [Other-IDs] NLM/ PMC1955082
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47. Kachalo S, Zhang R, Sontag E, Albert R, DasGupta B: NET-SYNTHESIS: a software for synthesis, inference and simplification of signal transduction networks. Bioinformatics; 2008 Jan 15;24(2):293-5
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  • We illustrate the biological usability of our software by applying it to a previously published signal transduction network and by using it to synthesize and simplify a novel network corresponding to activation-induced cell death in large granular lymphocyte leukemia.

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  • (PMID = 18033793.001).
  • [ISSN] 1367-4811
  • [Journal-full-title] Bioinformatics (Oxford, England)
  • [ISO-abbreviation] Bioinformatics
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, U.S. Gov't, Non-P.H.S.
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Proteome
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48. Souabni A, Jochum W, Busslinger M: Oncogenic role of Pax5 in the T-lymphoid lineage upon ectopic expression from the immunoglobulin heavy-chain locus. Blood; 2007 Jan 1;109(1):281-9
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  • The B-lymphoidPAX5 gene participates in the generation of the t(9;14)(p13;q32) translocation in germinal center B cells, which leads to deregulated PAX5 expression under the control of the immunoglobulin heavy-chain (IgH) locus in a subset of B-cell non-Hodgkin lymphomas.
  • The IgH(P5ki) allele, which corresponds to a germline rather than somatic mutation, is activated in multipotent hematopoietic progenitors and is subsequently expressed in dendritic cells (DCs) and in natural killer (NK), T, and B cells.
  • Ectopic Pax5 expression interferes with normal T-cell development and causes immature T-lymphoblastic lymphomas in IgH(P5ki/+) and IgH(P5ki/P5ki) mice.
  • Aggressive T-cell lymphomas develop even faster in Ik(Pax5/+) mice expressing Pax5 from the Ikaros locus.
  • Pax5 expression in thymocytes activates B-cell-specific genes and represses T-lymphoid genes, suggesting that Pax5 contributes to lymphomagenesis by deregulating the T-cell gene-expression program.
  • [MeSH-major] B-Cell-Specific Activator Protein / physiology. Cell Differentiation / genetics. Cell Transformation, Neoplastic / genetics. Chromosomes, Human, Pair 14 / genetics. Chromosomes, Human, Pair 9 / genetics. Immunoglobulin Heavy Chains / genetics. Neoplastic Stem Cells / pathology. Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics. Promoter Regions, Genetic. T-Lymphocytes / pathology. Translocation, Genetic
  • [MeSH-minor] Alleles. Animals. B-Lymphocytes / metabolism. B-Lymphocytes / pathology. Bone Marrow Transplantation. Cell Lineage. Dendritic Cells / metabolism. Dendritic Cells / pathology. Embryonal Carcinoma Stem Cells. Gene Expression Regulation, Neoplastic. Humans. Ikaros Transcription Factor / genetics. Killer Cells, Natural / metabolism. Killer Cells, Natural / pathology. Lymphocytes / metabolism. Lymphocytes / pathology. Lymphoma, B-Cell / genetics. Lymphoma, B-Cell / pathology. Mice. Mice, Inbred C57BL. Mutagenesis, Insertional. Neoplasm Transplantation. Radiation Chimera

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  • (PMID = 16968900.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / B-Cell-Specific Activator Protein; 0 / Immunoglobulin Heavy Chains; 0 / PAX5 protein, human; 0 / Pax5 protein, mouse; 0 / Zfpn1a1 protein, mouse; 148971-36-2 / Ikaros Transcription Factor
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49. Wong T, Ko JY, Wang FS, Chen YJ, Ma MC: Epstein-Barr virus associated extranodal natural killer T cell lymphoma of nasal type mimicking pyogenic osteomyelitis of the proximal humerus. Chang Gung Med J; 2008 May-Jun;31(3):314-9
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  • [Title] Epstein-Barr virus associated extranodal natural killer T cell lymphoma of nasal type mimicking pyogenic osteomyelitis of the proximal humerus.
  • Extranodal natural killer (NK) cell lymphoma/leukemia, nasal type, is rare but highly aggressive.
  • We report a male patient who suffered from EBV associated NK/T cell lymphoma of the proximal humerus but presented as pyogenic osteomyelitis with the clinical signs and symptoms of fever, local erythema, elevated erythrocyte sedimation rate and C-reactive protein.
  • The patient developed tumor recurrence and died due to pneumonia and respiratory failure 10 months after the initial diagnosis.
  • [MeSH-major] Epstein-Barr Virus Infections / complications. Humerus. Lymphoma, Extranodal NK-T-Cell / diagnosis. Osteomyelitis / diagnosis
  • [MeSH-minor] Adult. Diagnosis, Differential. Humans. Male. Suppuration

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  • (PMID = 18782956.001).
  • [ISSN] 2072-0939
  • [Journal-full-title] Chang Gung medical journal
  • [ISO-abbreviation] Chang Gung Med J
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] China (Republic : 1949- )
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50. Friedman J, Schattner A, Shvidel L, Berrebi A: Characterization of T-cell large granular lymphocyte leukemia associated with Sjogren's syndrome-an important but under-recognized association. Semin Arthritis Rheum; 2006 Apr;35(5):306-11
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  • [Title] Characterization of T-cell large granular lymphocyte leukemia associated with Sjogren's syndrome-an important but under-recognized association.
  • OBJECTIVE: Patients with T-cell (CD3+) large granular lymphocyte (LGL) leukemia have a high prevalence of autoantibodies and associated autoimmune diseases.
  • We set to determine the prevalence of Sjogren's syndrome in LGL leukemia and its cytokine profile.
  • METHODS: Every patient with a confirmed diagnosis of LGL leukemia diagnosed at a single academic medical center over the last 15 years was evaluated for Sjogren's syndrome by questioning about sicca symptoms.
  • Supernatants obtained from T-LGL leukemic cells following phytohemagglutinin (PHA) activation were analyzed for cytokine production by enzyme-linked immunosorbent assay and patients with or without Sjogren's syndrome were compared with controls.
  • Supernatants of T-LGL leukemia cells incubated with PHA revealed markedly increased levels of multiple cytokines (especially soluble interleukin 2 receptor, tumor necrosis factor alpha, IL-6, IL-8) compared with healthy controls.
  • However, this increase was common to LGL leukemia patients with or without Sjogren's syndrome.
  • CONCLUSIONS: Sjogren's syndrome was commonly identified in the patients with T-cell LGL leukemia in this study.
  • [MeSH-major] Leukemia, T-Cell / epidemiology. Sjogren's Syndrome / epidemiology
  • [MeSH-minor] Adult. Aged. Autoantibodies / immunology. Cytokines / immunology. Female. Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor. Humans. Male. Middle Aged. Prevalence


51. Ma R, Xu YG, Yang XH, Hu XM, Li L, Tang XD, Zhang SS, Xu S, Wang HZ, Liu F: [Immunophenotypic features in leukemia of NK cell series]. Zhongguo Shi Yan Xue Ye Xue Za Zhi; 2006 Feb;14(1):35-8
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  • [Title] [Immunophenotypic features in leukemia of NK cell series].
  • The aim was to investigate the immunophenotypes of NK series leukemia.
  • Immunophenotypes of 297 cases of acute leukemia (AL) were measured by flow cytometry, and these immucopenotypic features were analyzed.
  • 6 cases were NK series leukemia and 37 cases were acute myelogenous leukemia with CD56 expressed.
  • One patient has been diagnosed as myeloid/NK cell precursor acute leukemia, two patients were blastic NK cell leukemia, one was supposed to be NK-like T-cell lymphoma/leukemia, while another one was large granular lymphocyte leukemia (LGLL).
  • It is concluded that almost all of CD56 positive leukemia were acute myelogenous leukemia with CD56 expressed.
  • The immunophenotypes of NK series leukemia were antigens from hematopoietic stem cells to T/NK progenitor cells with meyloid antigen positive, and through NK progenitors to mature NK cells.
  • The immunophenotypes of heterogeneous NK leukemia cells are different, that should be carefully distinguished.

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  • (PMID = 16584587.001).
  • [ISSN] 1009-2137
  • [Journal-full-title] Zhongguo shi yan xue ye xue za zhi
  • [ISO-abbreviation] Zhongguo Shi Yan Xue Ye Xue Za Zhi
  • [Language] CHI
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] China
  • [Chemical-registry-number] 0 / Antigens, CD56
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52. Bang SM, Kim YK, Park YH, Sohn SK, Lee JJ, Cho EK, Ryoo BY, Chung IJ, Yoon SS, Kim HJ, Lee JH, Yoon HJ, Park S: High-dose therapy and autologous stem cell transplantation in Korean patients with aggressive T/NK-cell lymphoma. Leuk Lymphoma; 2005 Nov;46(11):1599-1604
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  • [Title] High-dose therapy and autologous stem cell transplantation in Korean patients with aggressive T/NK-cell lymphoma.
  • The proportion of aggressive T/NK-cell lymphoma in Korea is larger than in the West, and it shows a lower response to conventional chemotherapy and poorer survival than diffuse large B-cell lymphoma.
  • This study was undertaken to evaluate the response rate and survival and to document the prognostic factors in patients with T/NK-cell lymphoma who have undergone high-dose therapy (HDT).
  • Eligibility for the study was a mature T/NK-cell lymphoma with initially poor risk (as high or high intermediate risk on age-adjusted International Prognostic Index) or relapsed cases.
  • Twelve patients had unspecified peripheral T-cell lymphomas, 7 anaplastic large-cell lymphomas, 6 nasal T/NK-cell lymphomas, and 3 angioimmunoblastic T-cell lymphomas.
  • Disease status at transplant were initially poor risk in 15, chemosensitive relapse in 8 and chemo-resistant relapse in 5 patients, respectively.
  • Absolute neutrophil count ( > 500/microl) recovered at a median 11 days after autologous stem cell transplantation in 26 patients.
  • Therefore, an initial approach with effective induction and HDT may result in a better outcome in T/NK-cell lymphoma.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / administration & dosage. Hematopoietic Stem Cell Transplantation / methods. Killer Cells, Natural / pathology. Lymphoma, T-Cell / therapy

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  • (PMID = 16334486.001).
  • [ISSN] 1042-8194
  • [Journal-full-title] Leukemia & lymphoma
  • [ISO-abbreviation] Leuk. Lymphoma
  • [Language] eng
  • [Publication-type] Journal Article; Multicenter Study
  • [Publication-country] England
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53. Kwong YL: Hematopoietic stem cell transplantation in natural killer cell lymphoma and leukemia. Int J Hematol; 2010 Dec;92(5):702-7
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  • [Title] Hematopoietic stem cell transplantation in natural killer cell lymphoma and leukemia.
  • Natural killer (NK) cell lymphomas and leukemias are aggressive neoplasms.
  • Clinically, they can be classified into nasal, non-nasal and lymphoma/leukemia subtypes.
  • High-dose chemotherapy and hematopoietic stem cell transplantation (HSCT) may improve patient outcome.
  • For autologous HSCT, a critical review of the literature shows that most patients with nasal NK cell lymphoma in complete remission (CR) appear to do well without HSCT.
  • Therefore, identification of patients with nasal NK cell lymphoma in CR who are at high risk of relapse may be necessary before autologous HSCT can be recommended.
  • Patients with disseminated nasal NK cell lymphoma, non-nasal NK cell lymphoma and NK cell leukemia have poor outcome with autologous HSCT.
  • Continuous efforts should be devoted to risk stratification for identifying high-risk individuals for HSCT, and defining the optimal conditioning regimen for NK cell lymphomas.
  • [MeSH-major] Hematopoietic Stem Cell Transplantation. Killer Cells, Natural / pathology. Leukemia / therapy. Lymphoma / therapy

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  • (PMID = 21107769.001).
  • [ISSN] 1865-3774
  • [Journal-full-title] International journal of hematology
  • [ISO-abbreviation] Int. J. Hematol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] Japan
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54. Johansson AS, Norén-Nyström U, Larefalk A, Holmberg D, Lindskog M: Fish oil delays lymphoma progression in the TLL mouse. Leuk Lymphoma; 2010 Nov;51(11):2092-7
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  • The objective was to investigate the effects of omega-3 fatty acids, known for their anti-inflammatory effects, on time to lymphoma progression and survival in the TLL mouse, a strain genetically prone to developing aggressive T-cell lymphoma.
  • Compared to mice fed a standard diet, TLL mice fed omega-3 (menhaden fish oil) experienced a significant delay in disease progression and were more likely to remain alive and symptom free during the first 8 months of the study.
  • Immunological analysis demonstrated a significantly altered B-cell compartment and fewer NK cells in healthy C57Black6 mice fed omega-3, compared to controls.
  • [MeSH-major] Fish Oils / pharmacology. Lymphoma, T-Cell / prevention & control
  • [MeSH-minor] Animals. B-Lymphocytes / drug effects. B-Lymphocytes / pathology. Corn Oil / pharmacology. Dietary Fats / pharmacology. Disease Models, Animal. Disease Progression. Fatty Acids, Omega-3 / pharmacology. Female. Killer Cells, Natural / drug effects. Killer Cells, Natural / pathology. Male. Mice. Mice, Inbred C57BL. Time Factors

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  • (PMID = 20919854.001).
  • [ISSN] 1029-2403
  • [Journal-full-title] Leukemia & lymphoma
  • [ISO-abbreviation] Leuk. Lymphoma
  • [Language] eng
  • [Publication-type] Comparative Study; Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Dietary Fats; 0 / Fatty Acids, Omega-3; 0 / Fish Oils; 8001-30-7 / Corn Oil
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55. Kildahl-Andersen O: [Large granular lymphocyte leukemia]. Tidsskr Nor Laegeforen; 2009 Aug 27;129(16):1660; author reply 1660
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] [Large granular lymphocyte leukemia].
  • [MeSH-major] Leukemia, Large Granular Lymphocytic
  • [MeSH-minor] Arthritis, Rheumatoid / complications. Arthritis, Rheumatoid / diagnosis. Diagnosis, Differential. Felty Syndrome / complications. Felty Syndrome / diagnosis. Humans

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  • [CommentOn] Tidsskr Nor Laegeforen. 2009 May 28;129(11):1098-102 [19488091.001]
  • (PMID = 19721490.001).
  • [ISSN] 0807-7096
  • [Journal-full-title] Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række
  • [ISO-abbreviation] Tidsskr. Nor. Laegeforen.
  • [Language] nor
  • [Publication-type] Comment; Letter
  • [Publication-country] Norway
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56. Hofmann A, Zaharatos G, Miller M: Case report and review of the literature: Toxoplasma gondii encephalitis in a 40-year-old woman with common variable immunodeficiency and a new diagnosis of large granular lymphocytic leukemia. Can J Infect Dis Med Microbiol; 2008 Jul;19(4):309-10
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  • [Title] Case report and review of the literature: Toxoplasma gondii encephalitis in a 40-year-old woman with common variable immunodeficiency and a new diagnosis of large granular lymphocytic leukemia.
  • The present study describes a case of central nervous system toxoplasmosis in a patient with common variable immunodeficiency and newly diagnosed large granular lymphocytic leukemia, with a review of the literature for this association.

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  • (PMID = 19436513.001).
  • [ISSN] 1712-9532
  • [Journal-full-title] The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale
  • [ISO-abbreviation] Can J Infect Dis Med Microbiol
  • [Language] ENG
  • [Publication-type] Journal Article
  • [Publication-country] Egypt
  • [Other-IDs] NLM/ PMC2604779
  • [Keywords] NOTNLM ; Cerebral toxoplasmosis / Common variable immunodeficiency / Large granular lymphocytic leukemia / Toxoplasma gondii
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57. Kitchen BJ, Boxer LA: Large granular lymphocyte leukemia (LGL) in a child with hyper IgM syndrome and autoimmune hemolytic anemia. Pediatr Blood Cancer; 2008 Jan;50(1):142-5
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  • [Title] Large granular lymphocyte leukemia (LGL) in a child with hyper IgM syndrome and autoimmune hemolytic anemia.
  • Flow cytometry of the peripheral blood revealed the presence of a marked predominance of cytotoxic T lymphocytes, shown to be clonal, with concomitant natural killer (NK) antigen expression.
  • [MeSH-major] Anemia, Hemolytic, Autoimmune / complications. Hyper-IgM Immunodeficiency Syndrome / complications. Leukemia, Large Granular Lymphocytic / complications


58. Yamaguchi M, Suzuki R, Kwong YL, Kim WS, Hasegawa Y, Izutsu K, Suzumiya J, Okamura T, Nakamura S, Kawa K, Oshimi K: Phase I study of dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy for advanced-stage, relapsed or refractory extranodal natural killer (NK)/T-cell lymphoma and leukemia. Cancer Sci; 2008 May;99(5):1016-20
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  • [Title] Phase I study of dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy for advanced-stage, relapsed or refractory extranodal natural killer (NK)/T-cell lymphoma and leukemia.
  • Extranodal natural killer (NK)/T-cell lymphoma, nasal type, and aggressive NK-cell leukemia are rare, and their standard therapy has not been established.
  • They are Epstein-Barr virus-associated lymphoid malignancies, and tumor cells express P-glycoprotein leading to multidrug resistance of the disease.
  • Etoposide shows both in vitro and in vivo efficacy for Epstein-Barr virus-associated lymphoproliferative disorders.
  • At level 1, six patients with extranodal NK/T-cell lymphoma, nasal type, were enrolled.
  • Their disease status was newly diagnosed stage IV (n = 3), first relapse (n = 2), and primary refractory (n = 1).
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Leukemia, Lymphoid / drug therapy. Lymphoma, Extranodal NK-T-Cell / drug therapy

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  • (PMID = 18294294.001).
  • [ISSN] 1349-7006
  • [Journal-full-title] Cancer science
  • [ISO-abbreviation] Cancer Sci.
  • [Language] eng
  • [Publication-type] Clinical Trial, Phase I; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 6PLQ3CP4P3 / Etoposide; 7S5I7G3JQL / Dexamethasone; EC 3.5.1.1 / Asparaginase; UM20QQM95Y / Ifosfamide; YL5FZ2Y5U1 / Methotrexate
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59. van Steensel MA, van Gelder M, van Marion AM, Kremer B, Frank J: T-cell large granular lymphocytic leukaemia with an uncommon clinical and immunological phenotype. Acta Derm Venereol; 2009;89(2):172-4
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  • [Title] T-cell large granular lymphocytic leukaemia with an uncommon clinical and immunological phenotype.
  • Histopathological examination and peripheral blood analysis both showed a population of T-cell large granular lymphocytes, which were CD1+, CD2+, CD5+, CD7+ and CD16+, with expression of cutaneous lymphocyte-associated antigen.
  • Further laboratory examination revealed severe neutropaenia, relative lymphocytosis and a clonally rearranged T-cell receptor.
  • The cutaneous manifestation of T-cell large granular lymphocytic leukaemia is very rare.
  • In this particular patient, however, it was instrumental in establishing the diagnosis and may have been enabled by the expression of cutaneous lymphocyte-associated antigen on the cell surface.
  • [MeSH-major] Leukemia, Large Granular Lymphocytic / pathology. Skin Neoplasms / pathology
  • [MeSH-minor] Adult. Antigens, Differentiation, T-Lymphocyte. Antigens, Neoplasm / analysis. Cheek. Humans. Lymphocyte Subsets. Male. Membrane Glycoproteins / analysis. Skin / immunology

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  • (PMID = 19326004.001).
  • [ISSN] 0001-5555
  • [Journal-full-title] Acta dermato-venereologica
  • [ISO-abbreviation] Acta Derm. Venereol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Sweden
  • [Chemical-registry-number] 0 / Antigens, Differentiation, T-Lymphocyte; 0 / Antigens, Neoplasm; 0 / CTAGE1 protein, human; 0 / Membrane Glycoproteins
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60. Liang X, Graham DK: Natural killer cell neoplasms. Cancer; 2008 Apr 1;112(7):1425-36
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  • [Title] Natural killer cell neoplasms.
  • Natural killer (NK) cell tumors are an uncommon and heterogeneous group of disorders.
  • The World Health Organization (WHO) classified mature NK cell neoplasms into 2 types:.
  • 1) extranodal NK cell lymphoma, nasal type and 2) aggressive NK cell leukemia.
  • The mature NK cell tumors are prevalent in Asia and Central and South America.
  • Although blastic NK cell lymphoma, currently referred to as CD4+/CD56+ hematodermic neoplasm, also was included in the NK cell lymphoma category in the WHO classification scheme, existing evidence indicates a plasmacytoid dendritic cell derivation as opposed to an NK cell origin.
  • These tumors are characterized by blastic appearance, CD3-/CD4-/CD56+/CD13-/CD33- phenotype, T-cell receptor and immunoglobulin genes in germline configuration, and no evidence of EBV, suggesting a true immature NK cell derivation.
  • For this article, the authors reviewed the recent concepts and progress in clinicopathologic features, pathogenesis, genetic characteristics, diagnosis, differential diagnosis, treatment approaches, and outcomes of all subtypes of NK cell neoplasms.
  • [MeSH-major] Killer Cells, Natural / pathology. Leukemia / pathology. Lymphoma / pathology

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  • (PMID = 18286525.001).
  • [ISSN] 0008-543X
  • [Journal-full-title] Cancer
  • [ISO-abbreviation] Cancer
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Number-of-references] 103
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61. Nagata Y, Ohashi K, Fukuda S, Kamata N, Akiyama H, Sakamaki H: Clinical features of dasatinib-induced large granular lymphocytosis and pleural effusion. Int J Hematol; 2010 Jun;91(5):799-807
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  • [Title] Clinical features of dasatinib-induced large granular lymphocytosis and pleural effusion.
  • During follow-up of leukocyte counts in 20 consecutive patients (age range 29-81 years) treated with dasatinib, 9 patients (7 chronic myeloid leukemia in chronic phase, 2 Philadelphia chromosome-positive acute lymphoid leukemia in complete remission) developed lymphocytosis (>3,000/microl).
  • Peripheral blood smears revealed a population of large granular lymphocytes.
  • Large granular lymphocytosis (LGL) was first noted between 1 and 8 months after initiation of dasatinib, and it has persisted up to 33 months from the onset of LGL in one patient.
  • Peak numbers of large granular lymphocytes ranged from 2,915 to 17,425/microl.
  • The occurrence of LGL might interfere with achieving molecular response (MR, real-time quantification of major BCR-ABL1 mRNA less than 50 copies/microg RNA) in our small cohort; 8 (89%) of 9 patients with LGL attained MR, while only 6 (55%) of 11 patients without LGL eventually achieved MR.
  • With respect to the relationship between LGL and pleural effusion (PE), 3 (27%) of 11 patients without LGL developed PE, while 5 (56%) of 9 patients with LGL developed PE.
  • Moreover, the mean peak number of LGL was 9,215/microl, which was much higher than the mean peak number (4,635/microl) of LGL in patients without PE.
  • [MeSH-major] Leukemia, Large Granular Lymphocytic / chemically induced. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy. Pleural Effusion / chemically induced. Protein Kinase Inhibitors / adverse effects. Pyrimidines / adverse effects. Thiazoles / adverse effects
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Cohort Studies. Dasatinib. Female. Humans. Lymphocytes / pathology. Lymphocytosis / chemically induced. Male. Middle Aged

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  • (PMID = 20405252.001).
  • [ISSN] 1865-3774
  • [Journal-full-title] International journal of hematology
  • [ISO-abbreviation] Int. J. Hematol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Protein Kinase Inhibitors; 0 / Pyrimidines; 0 / Thiazoles; RBZ1571X5H / Dasatinib
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62. Iqbal J, Kucuk C, Deleeuw RJ, Srivastava G, Tam W, Geng H, Klinkebiel D, Christman JK, Patel K, Cao K, Shen L, Dybkaer K, Tsui IF, Ali H, Shimizu N, Au WY, Lam WL, Chan WC: Genomic analyses reveal global functional alterations that promote tumor growth and novel tumor suppressor genes in natural killer-cell malignancies. Leukemia; 2009 Jun;23(6):1139-51
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  • [Title] Genomic analyses reveal global functional alterations that promote tumor growth and novel tumor suppressor genes in natural killer-cell malignancies.
  • Natural killer (NK)-cell malignancies are among the most aggressive lymphoid neoplasms with very poor prognosis.
  • We performed array comparative genomic hybridization analysis on a number of NK cell lines and primary tumors to gain better understanding of the pathogenesis and tumor biology of these malignancies.
  • We also obtained transcriptional profiles of genes residing in these regions and compared them with normal and activated NK cells.
  • Genes downregulated in regions of loss included many transcription factors or repressors, tumor suppressors or negative regulators of the cell cycle.
  • Reversal of methylation by Decitabine induced expression of PRDM1 and cell death.
  • [MeSH-major] Comparative Genomic Hybridization. Crystallins / genetics. Gene Expression Regulation, Neoplastic. Genes, Tumor Suppressor. Killer Cells, Natural / pathology. Lymphoma / genetics. Membrane Proteins / genetics. Microtubule-Associated Proteins / genetics. Repressor Proteins / genetics
  • [MeSH-minor] Adult. Aged. Cell Proliferation. Chromosomes, Human, Pair 6. Gene Expression Profiling. Humans. Middle Aged. Tumor Cells, Cultured

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  • (PMID = 19194464.001).
  • [ISSN] 1476-5551
  • [Journal-full-title] Leukemia
  • [ISO-abbreviation] Leukemia
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / 5 U01 CA114778; United States / NCRR NIH HHS / RR / P20 RR016469
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / AIM1 protein, human; 0 / ATG5 protein, human; 0 / Crystallins; 0 / Membrane Proteins; 0 / Microtubule-Associated Proteins; 0 / Repressor Proteins; 138415-26-6 / PRDM1 protein, human
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63. Patel AP, Ghatak SB, Patel JA: Long term survival in aggressive NK cell leukemia. Indian Pediatr; 2010 Sep;47(9):807-8
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  • [Title] Long term survival in aggressive NK cell leukemia.
  • Aggressive natural killer cell leukemia (ANKL) is a rare type of leukemia.
  • [MeSH-major] Leukemia, Large Granular Lymphocytic / drug therapy. Leukemia, Large Granular Lymphocytic / pathology
  • [MeSH-minor] Adolescent. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Disease-Free Survival. Humans. Male. Prognosis. Remission Induction

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  • [CommentIn] Indian Pediatr. 2011 Jan;48(1):79-80 [21317480.001]
  • (PMID = 21048272.001).
  • [ISSN] 0974-7559
  • [Journal-full-title] Indian pediatrics
  • [ISO-abbreviation] Indian Pediatr
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] India
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64. Lai DW, Loughran TP Jr, Maciejewski JP, Sasu S, Song SX, Epling-Burnette PK, Paquette RL: Acquired amegakaryocytic thrombocytopenia and pure red cell aplasia associated with an occult large granular lymphocyte leukemia. Leuk Res; 2008 May;32(5):823-7
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  • [Title] Acquired amegakaryocytic thrombocytopenia and pure red cell aplasia associated with an occult large granular lymphocyte leukemia.
  • Acquired amegakaryocytic thrombocytopenia and pure red cell aplasia rarely occur concurrently.
  • We report a case in which these disorders were associated with an occult large granular lymphocyte leukemia.
  • Large granular lymphocyte leukemia should be suspected in the setting of unexplained bone marrow failure.
  • [MeSH-major] Leukemia, Large Granular Lymphocytic / complications. Purpura, Thrombocytopenic / complications. Red-Cell Aplasia, Pure / complications


65. Chang ST, Hsieh YC, Chen CH, Tsao CJ, Chuang SS: T-cell large granular lymphocytic leukemia with pleomorphic nuclei and colonic infiltration with chronic diarrhea. Leuk Lymphoma; 2010 Nov;51(11):2132-4
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  • [Title] T-cell large granular lymphocytic leukemia with pleomorphic nuclei and colonic infiltration with chronic diarrhea.
  • [MeSH-major] Colon / pathology. Diarrhea / etiology. Leukemia, Large Granular Lymphocytic / complications. Leukemia, Large Granular Lymphocytic / pathology. Leukemic Infiltration / complications
  • [MeSH-minor] Adult. Cell Nucleus / pathology. Chronic Disease. Colonic Neoplasms / secondary. Humans. Male. Neoplasm Invasiveness


66. Dinçol G, Palandüz S, Nalçaci M, Uçur A, Büyükaydin B: Myeloid/natural killer cell precursor acute leukemia with tetraploidy. Cancer Genet Cytogenet; 2005 Dec;163(2):156-9
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  • [Title] Myeloid/natural killer cell precursor acute leukemia with tetraploidy.
  • Myeloid/natural killer (NK) cell precursor acute leukemia is characterized by coexpression of myeloid and natural killer cell antigens and an aggressive clinical course.
  • Here we report a case of myeloid/NK precursor acute leukemia in a 37-year-old woman.
  • Peripheral blood smears and bone marrow aspirate smears at presentation revealed blastic cells, which were generally L2 shaped, with variation in cell size, round to moderately irregular nuclei and prominent nucleoli, pale cytoplasm, and a lack of azurophilic granules.
  • Immunophenotypic analysis of the blasts displayed coexpression of myeloid and natural killer cell antigens with relatively immature phenotype: CD7+, CD33+, CD34+, CD56+, CD57+, CD16-, MPO-.
  • To our knowledge, this is the first description of tetraploidy in myeloid/NK cell precursor acute leukemia.
  • [MeSH-major] Killer Cells, Natural / immunology. Leukemia, Myeloid / genetics. Polyploidy
  • [MeSH-minor] Acute Disease. Adult. Female. Humans. Immunophenotyping. In Situ Hybridization, Fluorescence. Karyotyping

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  • (PMID = 16337859.001).
  • [ISSN] 0165-4608
  • [Journal-full-title] Cancer genetics and cytogenetics
  • [ISO-abbreviation] Cancer Genet. Cytogenet.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
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67. Lazaro E, Caubet O, Menard F, Pellegrin JL, Viallard JF: [Large granular lymphocyte leukemia]. Presse Med; 2007 Nov;36(11 Pt 2):1694-700
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  • [Title] [Large granular lymphocyte leukemia].
  • [Transliterated title] Leucémies à grands lymphocytes granuleux.
  • Large granular lymphocyte (LGL) leukemia is a clonal proliferation of cytotoxic cells, either CD3(+) (T-cell) or CD3(-) (natural killer, or NK).
  • Both subtypes can manifest as indolent or aggressive disorders.
  • T-LGL leukemia is associated with cytopenias and autoimmune diseases and most often has an indolent course and good prognosis.
  • NK-LGL leukemias can be more aggressive.
  • LGL expansion is currently hypothesized to be a virus (Ebstein Barr or human T-cell leukemia viruses) antigen-driven T-cell response that involves disruption of apoptosis.
  • The diagnosis of T-LGL is suggested by flow cytometry and confirmed by T-cell receptor gene rearrangement studies.
  • Clonality is difficult to determine in NK-LGL but use of monoclonal antibodies specific for killer cell immunoglobulin-like receptor (KIR) has improved this process.
  • Treatment is required when T-LGL leukemia is associated with recurrent infections secondary to chronic neutropenia.
  • NK-LGL leukemias may be more aggressive and refractory to conventional therapy.
  • [MeSH-major] Leukemia, Large Granular Lymphocytic

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  • (PMID = 17596907.001).
  • [ISSN] 0755-4982
  • [Journal-full-title] Presse medicale (Paris, France : 1983)
  • [ISO-abbreviation] Presse Med
  • [Language] fre
  • [Publication-type] English Abstract; Journal Article; Review
  • [Publication-country] France
  • [Number-of-references] 35
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68. Sonoda K, Miyamoto S, Nakashima M, Wake N: Receptor-binding cancer antigen expressed on SiSo cells induces apoptosis via ectodomain shedding. Exp Cell Res; 2010 Jul 1;316(11):1795-803
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  • Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is a secreted antigen that induces apoptosis in putative receptor-expressing cells, including peripheral lymphocytes and natural killer (NK) cells.
  • RCAS1 expression is associated with aggressive characteristics and poor overall survival for 15 different human malignancies.
  • The cell lines SiSo and MCF-7, human uterine carcinoma and breast adenocarcinoma, respectively, both express RCAS1, but RCAS1 secretion is undetectable in MCF-7 cells.
  • Additionally, the RCAS1 putative receptor-expressing human chronic myelogenous leukemia cell line K562 was co-cultured with SiSo, MCF-7, or soluble RCAS1 to follow RCAS1 secretion in apoptosis initiation.
  • [MeSH-minor] Breast Neoplasms / immunology. Breast Neoplasms / pathology. Cell Line, Tumor. Coculture Techniques. Female. Humans. K562 Cells. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / immunology. Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology. MAP Kinase Signaling System. Phosphorylation. Signal Transduction. Tetradecanoylphorbol Acetate / pharmacology. Uterine Neoplasms / immunology. Uterine Neoplasms / pathology

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  • (PMID = 20079734.001).
  • [ISSN] 1090-2422
  • [Journal-full-title] Experimental cell research
  • [ISO-abbreviation] Exp. Cell Res.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antigens, Neoplasm; 0 / EBAG9 protein, human; NI40JAQ945 / Tetradecanoylphorbol Acetate
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69. Viny AD, Clemente MJ, Jasek M, Askar M, Ishwaran H, Nowacki A, Zhang A, Maciejewski JP: MICA polymorphism identified by whole genome array associated with NKG2D-mediated cytotoxicity in T-cell large granular lymphocyte leukemia. Haematologica; 2010 Oct;95(10):1713-21
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  • [Title] MICA polymorphism identified by whole genome array associated with NKG2D-mediated cytotoxicity in T-cell large granular lymphocyte leukemia.
  • BACKGROUND: Large granular lymphocyte leukemia is a semi-autonomous clonal proliferation of cytotoxic T cells accompanied by immune cytopenias and various autoimmune conditions.
  • Due to the rarity of this disease and its association with autoimmune diseases, a theoretical germline or somatic mutation might have significant penetrance, thus enabling detection, even from samples of suboptimal size, through genome-wide association studies.
  • DESIGN AND METHODS: To investigate a non-mendelian genetic predisposition to large granular lymphocyte leukemia, we used a step-wise method for gene discovery.
  • RESULTS: Our analysis found an association with MICA, a non-peptide-presenting, tightly regulated, stress-induced MHC-like molecule and cognate receptor for NKG2D, found abundantly on large granular lymphocyte leukemia cells.
  • Sequencing of germline DNA revealed a higher frequency of MICA*00801/A5.1 in patients with large granular lymphocyte leukemia than in matched controls (64% versus 41%, P<0.001, homozygous 40% versus 15%, P<0.001).
  • Flow cytometry was employed to determine the expression of MICA within hematologic compartments, showing that the signal intensity of MICA was increased in granulocytes from neutropenic patients with large granular lymphocyte leukemia in comparison with that in controls (P=0.033).
  • Finally, large granular lymphocyte leukemia cells were able to selectively kill MICA(+) Ba/F3 lymphocytes transfected with human MICA*019 in a dose-dependent manner compared to naïve cells (P<0.001), an effect mitigated by administration of an anti-NKG2D antibody (P=0.033).
  • CONCLUSIONS: Our results illustrate that MICA-NKG2D played a role in disease pathogenesis in the majority of patients in our cohort of cases of large granular lymphocyte leukemia and further investigation into this signaling axis may provide potent therapeutic targets.

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  • (PMID = 20460636.001).
  • [ISSN] 1592-8721
  • [Journal-full-title] Haematologica
  • [ISO-abbreviation] Haematologica
  • [Language] ENG
  • [Grant] United States / NHLBI NIH HHS / HL / K24 HL077522; United States / PHS HHS / / U54 655365070704; United States / Howard Hughes Medical Institute / / ; United States / PHS HHS / / R01 655365071402; United States / PHS HHS / / K24 655365071503
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] Italy
  • [Chemical-registry-number] 0 / Histocompatibility Antigens Class I; 0 / KLRK1 protein, human; 0 / MHC class I-related chain A; 0 / NK Cell Lectin-Like Receptor Subfamily K
  • [Other-IDs] NLM/ PMC2948097
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70. Choi YL, Moriuchi R, Osawa M, Iwama A, Makishima H, Wada T, Kisanuki H, Kaneda R, Ota J, Koinuma K, Ishikawa M, Takada S, Yamashita Y, Oshimi K, Mano H: Retroviral expression screening of oncogenes in natural killer cell leukemia. Leuk Res; 2005 Aug;29(8):943-9
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  • [Title] Retroviral expression screening of oncogenes in natural killer cell leukemia.
  • Aggressive natural killer cell leukemia (ANKL) is an intractable malignancy that is characterized by the outgrowth of NK cells.
  • To identify transforming genes in ANKL, we constructed a retroviral cDNA expression library from an ANKL cell line KHYG-1.
  • Mutation-specific PCR analysis indicated that the KRAS mutation was present only in KHYG-1 cells, not in another ANKL cell line or in clinical specimens (n=8).
  • [MeSH-major] Gene Expression Regulation, Leukemic. Genetic Testing / methods. Killer Cells, Natural / metabolism. Leukemia / genetics. Oncogenes. Proto-Oncogene Proteins / genetics. Retroviridae / genetics
  • [MeSH-minor] 3T3 Cells. Animals. Cell Line. DNA, Complementary / genetics. Gene Library. Humans. Mice. Mutation. Transfection. ras Proteins

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  • (PMID = 15978945.001).
  • [ISSN] 0145-2126
  • [Journal-full-title] Leukemia research
  • [ISO-abbreviation] Leuk. Res.
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / DNA, Complementary; 0 / KRAS protein, human; 0 / Proto-Oncogene Proteins; EC 3.6.5.2 / ras Proteins
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71. Isoda A, Tsukamoto N, Mitsui T, Yamane A, Hatsumi N, Matsushima T, Murakami H, Nojima Y, Karasawa M: Expression of CD55 and CD59 on peripheral blood cells in patients with lymphoproliferative disease of granular lymphocytes. Int J Lab Hematol; 2007 Feb;29(1):52-7
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  • [Title] Expression of CD55 and CD59 on peripheral blood cells in patients with lymphoproliferative disease of granular lymphocytes.
  • Lymphoproliferative disease of granular lymphocytes (LDGL) is a disorder characterized by the clonal expansion of granular lymphocytes.
  • It has recently been shown that the clonal expansion of granular lymphocytes occurs in patients with paroxysmal nocturnal hemoglobinuria (PNH) in a subclinical fashion.
  • An unexpected finding was the significantly lower CD55/59 expression on granular lymphocytes from patients with CD16(+)CD56(-) phenotype LDGL than from patients with CD16(+)CD56(+) phenotype LDGL, or natural killer (NK) and NK/T lymphocytes from healthy individuals.
  • The positive correlation between the expression of CD56 and CD55/59 might have some relevance to the functional properties of the CD56(+) subset of large granular lymphocytes.
  • [MeSH-major] Antigens, CD55 / biosynthesis. Antigens, CD59 / biosynthesis. Gene Expression Regulation. Killer Cells, Natural / metabolism. Lymphoproliferative Disorders / metabolism. T-Lymphocytes / metabolism

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  • (PMID = 17224008.001).
  • [ISSN] 1751-5521
  • [Journal-full-title] International journal of laboratory hematology
  • [ISO-abbreviation] Int J Lab Hematol
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antigens, CD55; 0 / Antigens, CD59; 101754-01-2 / CD59 protein, human
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72. Liu X, Ryland L, Yang J, Liao A, Aliaga C, Watts R, Tan SF, Kaiser J, Shanmugavelandy SS, Rogers A, Loughran K, Petersen B, Yuen J, Meng F, Baab KT, Jarbadan NR, Broeg K, Zhang R, Liao J, Sayers TJ, Kester M, Loughran TP Jr: Targeting of survivin by nanoliposomal ceramide induces complete remission in a rat model of NK-LGL leukemia. Blood; 2010 Nov 18;116(20):4192-201
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  • [Title] Targeting of survivin by nanoliposomal ceramide induces complete remission in a rat model of NK-LGL leukemia.
  • The natural killer (NK) type of aggressive large granular lymphocytic (LGL) leukemia is a fatal illness that pursues a rapid clinical course.
  • Here we report that the survivin was highly expressed in both aggressive and chronic leukemic NK cells but not in normal NK cells.
  • In vitro treatment of human and rat NK-LGL leukemia cells with cell-permeable, short-chain C₆-ceramide (C₆) in nanoliposomal formulation led to caspase-dependent apoptosis and diminished survivin protein expression, in a time- and dose-dependent manner.
  • Importantly, systemic intravenous delivery of nanoliposomal ceramide induced complete remission in the syngeneic Fischer F344 rat model of aggressive NK-LGL leukemia.
  • These data suggest that in vivo targeting of survivin through delivery of nanoliposomal C₆-ceramide may be a promising therapeutic approach for a fatal leukemia.

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  • (PMID = 20671121.001).
  • [ISSN] 1528-0020
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / R01 CA133525; United States / NCI NIH HHS / CA / R01 CA098472; United States / NCI NIH HHS / CA / CA133525; United States / NCI NIH HHS / CA / CA098472; United States / NCI NIH HHS / CA / N01CO12400
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Birc5 protein, rat; 0 / Ceramides; 0 / Liposomes; 0 / Microtubule-Associated Proteins; EC 2.7.11.24 / Extracellular Signal-Regulated MAP Kinases; EC 3.4.22.- / Caspases
  • [Other-IDs] NLM/ PMC2993625
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73. Manucha V, Zhao F, Rodgers W: Atypical lymphoid cells in cerebrospinal fluid in acute Epstein Barr virus infection: a case report demonstrating a pitfall in cerebrospinal fluid cytology. Acta Cytol; 2008 May-Jun;52(3):334-6
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  • BACKGROUND: Cytologic examination of cerebrospinal fluid (CSF) continues to be important in the diagnosis of malignancies involving the leptomeninges.
  • A well-recognized pitfall is overinterpretation of the presence of atypical lymphocytes that resemble malignant lymphoid cells in the CSF.
  • A definite diagnosis is often difficult because of limited viability of cells and small sample size of CSF.
  • CASE: A 25-year-old patient with a past history of treated large granular lymphocytic leukemia and presence of a predominant population of large, atypical lymphoid cells in the CSF, giving us the impression of involvement with large cell lymphoma.
  • CONCLUSION: The presence of atypical cells in the CSF certainly warrants a detailed look at the patient's laboratory investigations and communication with the hematologist, because it may be the only specimen available for diagnosis on which therapy and prognosis is based.
  • [MeSH-major] Cerebrospinal Fluid / cytology. Cytological Techniques / methods. Epstein-Barr Virus Infections / cerebrospinal fluid. Epstein-Barr Virus Infections / pathology. Lymphocytes / pathology
  • [MeSH-minor] Adult. DNA, Viral / analysis. DNA, Viral / blood. Hepatomegaly / ultrasonography. Humans. Leukemia, Large Granular Lymphocytic / drug therapy. Lymph Nodes / pathology. Lymph Nodes / radiography. Lymphatic Diseases / pathology. Lymphatic Diseases / radiography. Male. Pleural Effusion / radiography. Splenectomy

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  • (PMID = 18540300.001).
  • [ISSN] 0001-5547
  • [Journal-full-title] Acta cytologica
  • [ISO-abbreviation] Acta Cytol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / DNA, Viral
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74. Chang H, Kamel-Reid S, Hussain N, Lipton J, Messner HA: T-cell large granular lymphocytic leukemia of donor origin occurring after allogeneic bone marrow transplantation for B-cell lymphoproliferative disorders. Am J Clin Pathol; 2005 Feb;123(2):196-9
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  • [Title] T-cell large granular lymphocytic leukemia of donor origin occurring after allogeneic bone marrow transplantation for B-cell lymphoproliferative disorders.
  • T-cell lymphoproliferative disorders are uncommon occurrences after bone marrow transplantation (BMT).
  • We describe 2 patients in whom a monoclonal T-cell large granular lymphocytosis (T-LGL) developed after allogeneic BMT for B-cell lymphoproliferative disorders.
  • Both patients showed a persistent expansion of CD3+, CD8+, and CD57+ large granular lymphocytes of donor origin with clonally rearranged T-cell receptor gamma genes and no evidence of Epstein-Barr virus-related infection.
  • The manifestations were consistent with T-LGL leukemia as defined by the World Health Organization criteria.
  • In both patients, graft-vs-host disease developed, and 1 had recurrent episodes of cytomegalovirus viremia.
  • Both patients remain in complete remission from their B-cell lymphoproliferative disorders and do not have symptoms related to T-LGL leukemia.
  • These data show that T-LGL leukemia should be included as one of the types of posttransplantation lymphoproliferative disorders that can occur after allogeneic BMT for B-cell neoplasms.
  • [MeSH-major] Bone Marrow Transplantation / adverse effects. Leukemia, Lymphocytic, Chronic, B-Cell / therapy. Leukemia, T-Cell / pathology. Tissue Donors. Waldenstrom Macroglobulinemia / therapy
  • [MeSH-minor] Clone Cells. DNA, Neoplasm / analysis. Humans. Male. Middle Aged. Polymerase Chain Reaction. Receptors, Antigen, T-Cell, gamma-delta / genetics. Remission Induction. Transplantation, Homologous

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  • (PMID = 15842042.001).
  • [ISSN] 0002-9173
  • [Journal-full-title] American journal of clinical pathology
  • [ISO-abbreviation] Am. J. Clin. Pathol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / DNA, Neoplasm; 0 / Receptors, Antigen, T-Cell, gamma-delta
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75. Robak T: Emerging drugs for rarer chronic lymphoid leukemias. Expert Opin Emerg Drugs; 2008 Mar;13(1):95-118
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  • [Title] Emerging drugs for rarer chronic lymphoid leukemias.
  • BACKGROUND: Rarer indolent lymphoid leukemias include well defined mature B-cell and T-cell neoplasm with widely varying natural history and specific morphological, immunophenotypic and molecular characteristics.
  • Among these are prolymphocytic leukemia (PLL), hairy cell leukemia (HCL) and its variants, large granular lymphocyte leukemia (LGLL) and adult T-cell leukemia/lymphoma (ATLL).
  • OBJECTIVE: To present current therapies and emerging drugs potentially useful in the treatment of rarer chronic lymphoid leukemias.
  • Future research should focus on the novel therapeutic strategies based on the molecular pathogenic mechanisms and the development of new targeted therapies for each distinct chronic lymphoid leukemia.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Drugs, Investigational / therapeutic use. Leukemia, Lymphoid / drug therapy
  • [MeSH-minor] Animals. Chronic Disease. Humans

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  • (PMID = 18321151.001).
  • [ISSN] 1744-7623
  • [Journal-full-title] Expert opinion on emerging drugs
  • [ISO-abbreviation] Expert Opin Emerg Drugs
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Drugs, Investigational
  • [Number-of-references] 189
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76. Löffler H, Kosely F, Ho AD, Krämer A: [Blastic plasmacytoid dendritic cell neoplasm - a rare differential diagnosis of neoplastic skin infiltrations associated with systemic symptoms]. Dtsch Med Wochenschr; 2009 Sep;134(39):1927-30
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  • [Title] [Blastic plasmacytoid dendritic cell neoplasm - a rare differential diagnosis of neoplastic skin infiltrations associated with systemic symptoms].
  • Additional immunohistochemistry of the skin specimen as well as cytologic and flow cytometric examination of the bone marrow revealed an immature cell population expressing CD4 and CD56 which infiltrated both the dermis and, with an infiltration grade of about 85 %, the bone marrow.
  • DIAGNOSIS: Blastic plasmacytoid dendritic cell neoplasm (formerly known as blastic NK cell lymphoma).
  • CONCLUSION: The blastic plasmacytoid dendritic cell neoplasm is a rare, aggressive hematopoietic neoplasm most likely related to acute myeloid leukemia (AML).
  • Since cutaneous involvement is regularly present at diagnosis, the differential diagnosis of unexplained skin lesions should include this disease entity, especially if peripheral blood abnormalities are present.
  • [MeSH-major] Leukemia, Myeloid, Acute / diagnosis. Skin / pathology. Skin Neoplasms / diagnosis
  • [MeSH-minor] Aged. Antineoplastic Agents / therapeutic use. Biopsy. Bone Marrow / pathology. Diagnosis, Differential. Exanthema. Female. Flow Cytometry. Humans. Immunohistochemistry. Immunophenotyping. Pancytopenia. Prognosis. Remission Induction

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  • [Copyright] Georg Thieme Verlag KG Stuttgart, New York.
  • (PMID = 19760552.001).
  • [ISSN] 1439-4413
  • [Journal-full-title] Deutsche medizinische Wochenschrift (1946)
  • [ISO-abbreviation] Dtsch. Med. Wochenschr.
  • [Language] ger
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Antineoplastic Agents
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77. Viny AD, Lichtin A, Pohlman B, Loughran T, Maciejewski J: Chronic B-cell dyscrasias are an important clinical feature of T-LGL leukemia. Leuk Lymphoma; 2008 May;49(5):932-8
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  • [Title] Chronic B-cell dyscrasias are an important clinical feature of T-LGL leukemia.
  • T cell large granular lymphocyte leukemia (T-LGL) is characterised by semiautonomous proliferation of monoclonal cytotoxic T lymphocytes, which can result in neutropenia, splenomegaly, and is associated with various autoimmune disorders, particularly rheumatoid arthritis.
  • The coexistence of T-LGL leukemia with B cell abnormalities has previously been identified in case reports.
  • Analysis of 63 T-LGL patients revealed a frequent association with humoral immune system abnormalities.
  • We identified coexisting B cell dyscrasias in 17 T-LGL patients (27% of total), of whom 12 had monoclonal gammopathy of unknown significance (MGUS) (19%), and 5 had chronic lymphocytic leukemia (CLL) (8%).
  • The presence of both MGUS and CLL was found in 2 patients (3%) and follicular lymphoma was identified with MGUS in another T-LGL patient (2%).
  • Additionally, polyclonal hypergammaglobulinemia or hypogammaglobulinemia was found in 10 additional LGL leukemia patients bringing the total frequency of B cell abnormalities in T-LGL leukemia to 43% in our cohort.
  • The co-association of B cell pathology with T-LGL suggests that either a common antigen drives clonal B and T cells, or that humoral malignancy could serve as the stimulus for lymphocyte expansion representing an overactive anti-tumour surveillance.
  • [MeSH-major] B-Lymphocytes / pathology. Leukemia, Large Granular Lymphocytic / etiology. Lymphoproliferative Disorders / complications
  • [MeSH-minor] Agammaglobulinemia / complications. Comorbidity. Humans. Hypergammaglobulinemia / complications. Leukemia, Lymphocytic, Chronic, B-Cell / complications. Lymphoma, Follicular / complications. Monoclonal Gammopathy of Undetermined Significance / complications

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  • [CommentIn] Leuk Lymphoma. 2008 May;49(5):845-6 [18464104.001]
  • (PMID = 18452068.001).
  • [ISSN] 1029-2403
  • [Journal-full-title] Leukemia & lymphoma
  • [ISO-abbreviation] Leuk. Lymphoma
  • [Language] eng
  • [Grant] United States / Howard Hughes Medical Institute / /
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
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78. Thomas J, Haseman JK, Goodman JI, Ward JM, Loughran TP Jr, Spencer PJ: A review of large granular lymphocytic leukemia in Fischer 344 rats as an initial step toward evaluating the implication of the endpoint to human cancer risk assessment. Toxicol Sci; 2007 Sep;99(1):3-19
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  • [Title] A review of large granular lymphocytic leukemia in Fischer 344 rats as an initial step toward evaluating the implication of the endpoint to human cancer risk assessment.
  • Large granular lymphocyte leukemia (LGLL) is a common fatal disease in aging F344 rats.
  • The current understanding of rat LGLL and a search for mechanistic data/correlations to human leukemia were examined with the goal of improving evaluation of the LGLL endpoint in cancer bioassays as it relates to human cancer risk assessments.
  • The exact cell of origin of the F344 rat LGLL is not fully resolved, although natural killer (NK) cell characteristics were demonstrated in most, if not all cases.
  • Similarities between rat LGLL and a rare human NK-LGLL exist, invalidating claims of no human counterpart, although the underlying etiopathogenesis may be different.
  • There is insufficient data to establish a mode of action of chemical-induced rat LGLL.
  • Evaluation of the National Toxicology Program database revealed only 34 substances (out of over 500 studied) that were possibly associated with increased incidences of LGLL.
  • Of these, only five produced definitive LGLL effects in both sexes; the remaining 29 produced single sex responses and/or only "equivocal" associations with LGLL.
  • Trends of increasing background/variability in LGLL incidence and its modulation by extraneous factors (e.g., corn oil gavage) are key confounders in interpretation.
  • Given that LGLL is a common tumor in control F344 rats, interpretations of bioassays can be improved by increasing the statistical stringency (e.g., p<0.01 over traditional p<0.05), as an indicator of possible carcinogenic effects, but that alone would be insufficient evidence for declaring treatment-related increases.
  • Thus, it was concluded that the evaluation of possible chemically related increases in rat LGLL utilize a "weight-of-evidence" approach.
  • [MeSH-major] Carcinogenicity Tests / methods. Disease Models, Animal. Leukemia, Lymphoid / pathology

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  • (PMID = 17522071.001).
  • [ISSN] 1096-6080
  • [Journal-full-title] Toxicological sciences : an official journal of the Society of Toxicology
  • [ISO-abbreviation] Toxicol. Sci.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] United States
  • [Number-of-references] 84
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79. Sino-US Shanghai Leukemia Cooperative Group: [Aggressive NK-cell leukemia: report of nine cases and review of literature]. Zhonghua Xue Ye Xue Za Zhi; 2006 Feb;27(2):116-9
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  • [Title] [Aggressive NK-cell leukemia: report of nine cases and review of literature].
  • OBJECTIVE: To improve the diagnostic accuracy of aggressive NK-cell leukemia (ANKL).
  • The disease had an aggressive clinical course.
  • (2) Neutropenia, anemia and thrombocytopenia with high number of circulating large granular lymphocytes;.
  • (3) large granular lymphocytes infiltrated in bone marrow aspirate and core biopsy;.
  • No T-cell receptor (TCR) genes rearrangement;.
  • (7) Exclusion of other diseases with large granular lymphocytosis.
  • [MeSH-major] Leukemia, Large Granular Lymphocytic / diagnosis

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  • (PMID = 16732967.001).
  • [ISSN] 0253-2727
  • [Journal-full-title] Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi
  • [ISO-abbreviation] Zhonghua Xue Ye Xue Za Zhi
  • [Language] chi
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] China
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80. Nakano-Akamatsu S, Takahashi R, Sekioka Y, Hosokawa Y, Inaba T: CD20- and CD56-positive T-cell large granular lymphocyte leukemia in a human T-cell leukemia virus type 1 carrier. Int J Hematol; 2007 Nov;86(4):348-51
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  • [Title] CD20- and CD56-positive T-cell large granular lymphocyte leukemia in a human T-cell leukemia virus type 1 carrier.
  • A 60-year-old man was diagnosed with asymptomatic T-cell granular lymphocyte (T-LGL) leukemia in September 2006.
  • He was serologically positive for human T-cell leukemia virus type 1 (HTLV-1).
  • However, monoclonal integration of the HTLV-1 genome was not detected in the peripheral blood, suggesting that HTLV-1 did not contribute to the pathogenesis of T-LGL leukemia in the present case.
  • Phenotypically, neoplastic cells of our case were CD3+, CD4*, CD8+, CD16-, CD56+, CD57*, and T-cell receptor (TCR) alphabeta+.
  • This represented a unique case of T-LGL leukemia showing a typical clinical and phenotypic features.
  • [MeSH-major] Antigens, CD20 / metabolism. Antigens, CD56 / metabolism. Human T-lymphotropic virus 1 / physiology. Leukemia, Large Granular Lymphocytic / metabolism. Leukemia, Large Granular Lymphocytic / virology
  • [MeSH-minor] Flow Cytometry. Humans. Male. Middle Aged. Receptors, Antigen, T-Cell, alpha-beta / genetics. Receptors, Antigen, T-Cell, alpha-beta / metabolism

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  • (PMID = 18055343.001).
  • [ISSN] 0925-5710
  • [Journal-full-title] International journal of hematology
  • [ISO-abbreviation] Int. J. Hematol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Antigens, CD20; 0 / Antigens, CD56; 0 / Receptors, Antigen, T-Cell, alpha-beta
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81. Fortune AF, Kelly K, Sargent J, O'Brien D, Quinn F, Chadwick N, Flynn C, Conneally E, Browne P, Crotty GM, Thornton P, Vandenberghe E: Large granular lymphocyte leukemia: natural history and response to treatment. Leuk Lymphoma; 2010 May;51(5):839-45
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Large granular lymphocyte leukemia: natural history and response to treatment.
  • Large granular lymphocyte leukemia (T-LGL) is an indolent T lymphoproliferative disorder that was difficult to diagnose with certainty until clonality testing of the T cell receptor gene became routinely available.
  • We studied the natural history and response to treatment in 25 consecutive patients with T-LGL diagnosed between 2004 and 2008 in which the diagnosis was confirmed by molecular analysis, to define an effective treatment algorithm.
  • The median age at diagnosis was 61 years (range 27-78), with a male to female ratio of 1:1.8 and presenting features of fatigue (n = 13), recurrent infections (n = 9), and/or abnormal blood counts (n = 5).
  • Thirteen patients with symptomatic disease were treated as follows: pentostatin (nine patients), cyclosporine (six patients), methotrexate (three patients), and alemtuzumab in two patients in whom pentostatin was ineffective.
  • The overall survival (OS) and progression-free survival (PFS) 37 months from diagnosis were 80% and 52%, respectively.
  • Treatment of T-LGL should be reserved for patients with symptomatic disease, but in this series, pentostatin treatment was less toxic and more effective than cyclosporine or methotrexate.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Cyclosporine / therapeutic use. Immunosuppressive Agents / therapeutic use. Leukemia, Large Granular Lymphocytic / drug therapy

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  • Hazardous Substances Data Bank. PENTOSTATIN .
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  • (PMID = 20367569.001).
  • [ISSN] 1029-2403
  • [Journal-full-title] Leukemia & lymphoma
  • [ISO-abbreviation] Leuk. Lymphoma
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; 0 / Antibodies, Neoplasm; 0 / Immunosuppressive Agents; 395575MZO7 / Pentostatin; 3A189DH42V / alemtuzumab; 83HN0GTJ6D / Cyclosporine; YL5FZ2Y5U1 / Methotrexate
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82. Howe EC, Wlodarski M, Ball EJ, Rybicki L, Maciejewski JP: Killer immunoglobulin-like receptor genotype in immune-mediated bone marrow failure syndromes. Exp Hematol; 2005 Nov;33(11):1357-62
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  • [Title] Killer immunoglobulin-like receptor genotype in immune-mediated bone marrow failure syndromes.
  • OBJECTIVE: Recent reports have shown that killer immunoglobulin-like receptors (KIR) and KIR ligand (KIR-L) genotype play a role in the pathophysiology of autoimmune disorders.
  • The objective of this study is to establish the frequency of specific KIR genes and KIR-L alleles in aplastic anemia (AA), paroxysmal nocturnal hemoglobinuria (PNH), myelodysplasia (MDS), and large granular lymphocyte leukemia (LGL), as compared with healthy control patients.
  • METHODS: KIR genotyping was performed on DNA from 113 patients with AA, PNH, MDS, and LGL using sequence specific primer amplification.
  • [MeSH-minor] Anemia, Aplastic / genetics. Anemia, Aplastic / immunology. Case-Control Studies. Gene Frequency. Genotype. Hemoglobinuria, Paroxysmal / genetics. Hemoglobinuria, Paroxysmal / immunology. Histocompatibility Antigens Class I / genetics. Humans. Immunity. Leukemia, Lymphoid / genetics. Leukemia, Lymphoid / immunology. Ligands. Myelodysplastic Syndromes / genetics. Myelodysplastic Syndromes / immunology. Receptors, KIR. Syndrome

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  • (PMID = 16263420.001).
  • [ISSN] 0301-472X
  • [Journal-full-title] Experimental hematology
  • [ISO-abbreviation] Exp. Hematol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Netherlands
  • [Chemical-registry-number] 0 / Histocompatibility Antigens Class I; 0 / Ligands; 0 / Receptors, Immunologic; 0 / Receptors, KIR
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83. Subbiah V, Viny AD, Rosenblatt S, Pohlman B, Lichtin A, Maciejewski JP: Outcomes of splenectomy in T-cell large granular lymphocyte leukemia with splenomegaly and cytopenia. Exp Hematol; 2008 Sep;36(9):1078-83
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  • [Title] Outcomes of splenectomy in T-cell large granular lymphocyte leukemia with splenomegaly and cytopenia.
  • OBJECTIVE: T-cell large granular lymphocyte leukemia (T-LGL) is a chronic clonal lymphoproliferation of cytotoxic T cells often complicated by cytopenia.
  • Because the outcomes of splenectomy in patients with T-LGL have been only reported sporadically, we objectively assessed the outcomes of splenectomy.
  • MATERIALS AND METHODS: When a cohort of 56 T-LGL patients was analyzed, patients with splenomegaly (n = 34) and had higher frequency of bi- and pancytopenia than patients with no splenomegaly (70% vs 27%; p = 0.001).
  • Median spleen weight was 1300 g, consistent with diagnosis of splenomegaly; T-cell receptor (TCR)-gamma rearrangement and typical T-LGL were detected by immunophenotype in all specimens.
  • Two patients died due to causes possibly related to the splenectomized state and/or primary disease.
  • All patients showed lineage-specific hematologic response and achieved transfusion independence; however, precise molecular analysis of TCR and variable chain Vbeta flow cytometry showed persistence of the LGL clones.
  • CONCLUSION: We conclude that splenectomy constitutes a viable and safe therapeutic option for patients with T-LGL, splenomegaly, and refractory cytopenia.

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  • (PMID = 18550263.001).
  • [ISSN] 0301-472X
  • [Journal-full-title] Experimental hematology
  • [ISO-abbreviation] Exp. Hematol.
  • [Language] ENG
  • [Grant] United States / NHLBI NIH HHS / HL / K24 HL077522; United States / NCI NIH HHS / CA / R01 CA113972; United States / NCRR NIH HHS / RR / U54 RR019397; United States / Howard Hughes Medical Institute / /
  • [Publication-type] Comparative Study; Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Netherlands
  • [Other-IDs] NLM/ NIHMS67936; NLM/ PMC3537502
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84. Suzumiya J, Ohshima K, Tamura K, Karube K, Uike N, Tobinai K, Gascoyne RD, Vose JM, Armitage JO, Weisenburger DD, International Peripheral T-Cell Lymphoma Project: The International Prognostic Index predicts outcome in aggressive adult T-cell leukemia/lymphoma: analysis of 126 patients from the International Peripheral T-Cell Lymphoma Project. Ann Oncol; 2009 Apr;20(4):715-21
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] The International Prognostic Index predicts outcome in aggressive adult T-cell leukemia/lymphoma: analysis of 126 patients from the International Peripheral T-Cell Lymphoma Project.
  • BACKGROUND: The International Peripheral T-cell Lymphoma Project was organized to better understand the T-cell and natural killer (NK) cell lymphomas, and our task is to present the clinicopathologic correlations and therapeutic results for adult T-cell leukemia/lymphoma (ATL).
  • PATIENTS AND METHODS: Among 1153 patients with T-cell or NK cell lymphomas, 126 patients (9.6%) with ATL were represented in this project.
  • All were categorized as aggressive ATL, i.e. acute or lymphoma type, and 87% fell into the lymphoma type.
  • CONCLUSION: Patients with aggressive ATL have a poor clinical outcome and the IPI is a useful model for predicting outcome in ATL of the lymphoma type.

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  • (PMID = 19150954.001).
  • [ISSN] 1569-8041
  • [Journal-full-title] Annals of oncology : official journal of the European Society for Medical Oncology
  • [ISO-abbreviation] Ann. Oncol.
  • [Language] ENG
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Investigator] Savage K; Connors J; Gascoyne R; Chhanabhai M; Wilson W; Jaffe E; Armitage J; Vose J; Weisenburger D; Anderson J; Ullrich F; Bast M; Hochberg E; Harris N; Levine A; Nathwani B; Miller T; Rimsza L; Montserrat E; Lopez-Guillermo A; Campo E; Cuadros M; Alvarez Ferreira J; Martinez Delgado B; Holte H; Delabie J; Rüdiger T; Müller-Hermelink K; Reimer P; Adam P; Wilhelm M; Schmitz N; Nerl C; MacLennan KA; Zinzani PL; Pileri S; Federico M; Bellei M; Coiffier B; Berger F; Tanin I; Wannakrairot P; Au W; Liang R; Loong F; Rajan S; Sng I; Tobinai K; Matsuno Y; Morishima Y; Nakamura S; Seto M; Tanimoto M; Yoshino T; Suzumiya J; Ohshima K; Kim WS; Ko YH
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85. Shaw GR, Naik VS: The gammadelta variant of T cell large granular lymphocyte leukemia is very similar to the common alphabeta type: report of two cases. J Hematop; 2008 Sep;1(2):139-43
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  • [Title] The gammadelta variant of T cell large granular lymphocyte leukemia is very similar to the common alphabeta type: report of two cases.
  • The vast majority of cases of T cell large granular lymphocyte (T-LGL) leukemia have a CD3+, CD4-, CD8+ phenotype and express the alphabeta T cell receptor.
  • Two well-characterized cases of gammadelta T-LGL leukemia were identified by our laboratory in 2007.
  • These two cases and other reports of gammadelta T-LGL leukemia were compared with the common alphabeta variant.
  • Other than more often being negative for both CD4 and CD8 (in about 35% to 40% of cases), the gammadelta variant of T-LGL leukemia is similar to the common alphabeta type in virtually all respects and should be included in the general category of T-LGL leukemia.
  • However, it is important to exclude other more aggressive gammadelta T cell lymphoproliferative disorders.

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  • (PMID = 19669213.001).
  • [ISSN] 1868-9256
  • [Journal-full-title] Journal of hematopathology
  • [ISO-abbreviation] J Hematop
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Germany
  • [Other-IDs] NLM/ PMC2713487
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86. Sokol L, Loughran TP Jr: Large granular lymphocyte leukemia. Curr Hematol Malig Rep; 2007 Oct;2(4):278-82
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  • [Title] Large granular lymphocyte leukemia.
  • Clonal diseases of large granular lymphocytes (LGLs) represent a spectrum of clinically rare lymphoproliferative malignancies arising from either mature T-cell (CD3(+)) or natural killer (NK)-cell (CD3(-)) lineages.
  • The clinical behavior of these disorders ranges from indolent to very aggressive.
  • Patients with symptomatic indolent T-cell or NK-cell LGL leukemia are usually treated with immunosuppressive therapies; in contrast, aggressive T-cell or NK-cell LGL leukemias require intensive chemotherapy regimens.
  • [MeSH-major] Leukemia, Large Granular Lymphocytic
  • [MeSH-minor] Adolescent. Adult. Antibodies, Monoclonal / therapeutic use. Antibodies, Monoclonal, Humanized. Antibodies, Neoplasm / therapeutic use. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Child. Clinical Trials as Topic. Combined Modality Therapy. Disease Progression. Female. Humans. Immunophenotyping. Killer Cells, Natural / pathology. Leukemia, T-Cell / complications. Leukemia, T-Cell / epidemiology. Leukemia, T-Cell / immunology. Leukemia, T-Cell / pathology. Leukemia, T-Cell / therapy. Male. Middle Aged. Myelodysplastic Syndromes / pathology. Neutropenia / etiology. Opportunistic Infections / etiology. Stem Cell Transplantation

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  • (PMID = 20425381.001).
  • [ISSN] 1558-822X
  • [Journal-full-title] Current hematologic malignancy reports
  • [ISO-abbreviation] Curr Hematol Malig Rep
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
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  • [Number-of-references] 39
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87. Coppo P, Gouilleux-Gruart V, Huang Y, Bouhlal H, Bouamar H, Bouchet S, Perrot C, Vieillard V, Dartigues P, Gaulard P, Agbalika F, Douay L, Lassoued K, Gorin NC: STAT3 transcription factor is constitutively activated and is oncogenic in nasal-type NK/T-cell lymphoma. Leukemia; 2009 Sep;23(9):1667-78
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  • [Title] STAT3 transcription factor is constitutively activated and is oncogenic in nasal-type NK/T-cell lymphoma.
  • Nasal-type natural killer (NK) cell lymphoma is an infrequent aggressive malignant disease with very poor prognosis.
  • For this, we established and characterized a continuous interleukin 2-dependent NK cell line (MEC04) from a patient with a fatal nasal-type NK-cell lymphoma.
  • By using recombinant transducible TAT-STAT3-beta (beta isoform), TAT-STAT3Y705F (a STAT3 protein mutated on Y705 residue, which prevents STAT3 dimerization) and peptides inhibiting specifically STAT3 dimerization, we inhibited STAT3 phosphorylation and cell growth, with cell death induction.
  • Finally, STAT3 was phosphorylated in Y705 residue in the nuclei of lymphoma cells in eight/nine patients with nasal-type NK/T-cell lymphoma and in YT, another NK cell line.
  • Our results suggest that STAT3 protein has a major role in the oncogenic process of nasal-type NK-cell lymphomas, and may represent a promising therapeutical target.
  • [MeSH-major] Killer Cells, Natural / pathology. Lymphoma, T-Cell / etiology. Nose Neoplasms / etiology. STAT3 Transcription Factor / physiology

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  • (PMID = 19421230.001).
  • [ISSN] 1476-5551
  • [Journal-full-title] Leukemia
  • [ISO-abbreviation] Leukemia
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / BCL2L1 protein, human; 0 / STAT3 Transcription Factor; 0 / STAT3 protein, human; 0 / bcl-X Protein; 82115-62-6 / Interferon-gamma; EC 2.7.10.2 / JAK2 protein, human; EC 2.7.10.2 / Janus Kinase 2; EC 2.7.11.24 / Extracellular Signal-Regulated MAP Kinases
  • [Other-IDs] NLM/ HALMS419047; NLM/ PMC2796333
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88. Gill H, Liang RH, Tse E: Extranodal natural-killer/t-cell lymphoma, nasal type. Adv Hematol; 2010;2010:627401
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  • [Title] Extranodal natural-killer/t-cell lymphoma, nasal type.
  • The World Health Organization (WHO) classification recognizes 2 main categories of natural killer (NK) cell-derived neoplasms, namely, extranodal NK/T-cell lymphoma, nasal type, and aggressive NK-cell leukaemia.
  • Extranodal nasal NK/T-cell lymphoma is more frequent in the Far East and Latin America.
  • Early stage disease, in particular for localized lesion in the nasal region, is treated with chemotherapy and involved-field radiotherapy.
  • On the other hand, multiagent chemotherapy is the mainstay of treatment for advanced or disseminated disease.
  • The role of autologous hematopoietic stem cell transplantation is yet to be clearly defined.
  • Allogeneic hematopoietic stem cell transplantation, with the putative graft-versus-lymphoma effect, offers a potentially curative option in patients with advanced disease.

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  • (PMID = 21234094.001).
  • [ISSN] 1687-9112
  • [Journal-full-title] Advances in hematology
  • [ISO-abbreviation] Adv Hematol
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Other-IDs] NLM/ PMC3018635
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89. Epling-Burnette PK, Sokol L, Chen X, Bai F, Zhou J, Blaskovich MA, Zou J, Painter JS, Edwards TD, Moscinski L, Yoder JA, Djeu JY, Sebti S, Loughran TP Jr, Wei S: Clinical improvement by farnesyltransferase inhibition in NK large granular lymphocyte leukemia associated with imbalanced NK receptor signaling. Blood; 2008 Dec 1;112(12):4694-8
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  • [Title] Clinical improvement by farnesyltransferase inhibition in NK large granular lymphocyte leukemia associated with imbalanced NK receptor signaling.
  • Large granular lymphocyte (LGL) leukemia is commonly associated with poor hematopoiesis.
  • The first case of pulmonary artery hypertension (PAH) was observed in a 57-year-old woman with natural killer (NK)-LGL leukemia and transfusion-dependent anemia.
  • Using a genetic approach, we demonstrated that killing of pulmonary endothelial cells by patient NK cells was mediated by dysregulated balance in activating and inhibitory NK-receptor signaling.
  • Elevated pulmonary artery pressure and erythroid differentiation improved after disrupting the NK-receptor signaling pathway with 4 courses of a farnesyltransferase inhibitor, tipifarnib.
  • Coincidental association between PAH and LGL leukemia suggest a causal relationship between the expanded lymphocyte population and these clinical manifestations.

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  • (PMID = 18791165.001).
  • [ISSN] 1528-0020
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / R01 CA098472; United States / NCRR NIH HHS / RR / U54 RR019397; United States / NIAID NIH HHS / AI / AI056213; United States / NCI NIH HHS / CA / CA94872; United States / NCRR NIH HHS / RR / U54RR019397-05; United States / NCI NIH HHS / CA / CA11211201; United States / NIAID NIH HHS / AI / R01 AI056213
  • [Publication-type] Case Reports; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Enzyme Inhibitors; 0 / Quinolones; 0 / Receptors, Natural Killer Cell; 192185-72-1 / tipifarnib; EC 2.5.1.29 / Farnesyltranstransferase
  • [Other-IDs] NLM/ PMC2597136
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90. Takahashi T, Otani I, Okuda M, Inoue M, Ito K, Sakai M, Koie H, Yamaya Y, Watari T, Sato T, Kanayama K, Tokuriki M: Malignant transformation of T-cell large granular lymphocyte leukemia in a dog. J Vet Med Sci; 2007 Jun;69(6):677-81
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  • [Title] Malignant transformation of T-cell large granular lymphocyte leukemia in a dog.
  • An 8-year-old spayed female Golden Retriever was referred to us for evaluation of mild lymphocytosis.
  • The peripheral lymphocytes were comprised of mostly large granular lymphocytes (LGLs), and flow cytometry showed that they were mostly CD3+8+ T lymphocytes.
  • Clonal rearrangement of the T-cell receptor gene was identified in the peripheral blood, and the dog was therefore diagnosed with LGL chronic leukemia.
  • The dog was subclinical without treatment until hospitalization on day 154, at which point the lymphocytes looked like lymphoblasts and the surface markers changed to CD3-8-.
  • This was regarded as malignant transformation from LGL chronic leukemia to the acute type.
  • Necropsy revealed tumor cell infiltration into the heart, skin, and brain.

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  • (PMID = 17611371.001).
  • [ISSN] 0916-7250
  • [Journal-full-title] The Journal of veterinary medical science
  • [ISO-abbreviation] J. Vet. Med. Sci.
  • [Language] ENG
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Antineoplastic Agents
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91. Alekshun TJ, Sokol L: Diseases of large granular lymphocytes. Cancer Control; 2007 Apr;14(2):141-50
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  • [Title] Diseases of large granular lymphocytes.
  • BACKGROUND: Clonal diseases of large granular lymphocytes (LGLs) are rare lymphoproliferative malignancies that arise from either mature T-cell (CD3+) or natural killer (NK)-cell (CD3-) lineages.
  • They manifest a distinct biologic behavior that ranges from indolent to very aggressive.
  • METHODS: We discuss four distinct diseases involving LGLs: indolent T-cell LGL leukemia, aggressive T-cell LGL leukemia, chronic NK-cell leukemia, and aggressive NK-cell leukemia.
  • RESULTS: Sustained LGLs, characteristic immunophenotype, clonal origin of leukemic cells, and clinical presentation are the most important features that distinguish indolent from aggressive subtypes of LGL leukemia and guide the selection of therapy.
  • Patients with symptomatic indolent T-cell or NK-cell LGL leukemia are usually treated with immunosuppressive therapies in contrast to aggressive T-cell and NK-cell LGL leukemia, which require intensive chemotherapy induction regimens.
  • CONCLUSIONS: Future scientific advances focusing on the delineation of molecular pathogenic mechanisms and the development of new targeted therapies for each distinct LGL leukemia entity should lead to improved outcomes of patients with these disorders.
  • [MeSH-major] Antigens, CD3. Killer Cells, Natural / pathology. Leukemia, Lymphoid / pathology. Leukemia, T-Cell / pathology. Lymphocytes / pathology

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  • (PMID = 17387299.001).
  • [ISSN] 1073-2748
  • [Journal-full-title] Cancer control : journal of the Moffitt Cancer Center
  • [ISO-abbreviation] Cancer Control
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antigens, CD3
  • [Number-of-references] 71
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92. Gaur S, Mansoor S, Aish L: T-cell large granular lymphocytic leukemia and hereditary hemochromatosis: a fortuitous association? Am J Hematol; 2005 Apr;78(4):299-301
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  • [Title] T-cell large granular lymphocytic leukemia and hereditary hemochromatosis: a fortuitous association?
  • We describe a patient with hereditary hemochromatosis (homozygous for C282Y mutation) and neutropenia who was found to have underlying T-cell large granular lymphocytic (T-LGL) leukemia.
  • The diagnosis was confirmed by demonstrating T-cell receptor (TCR) gene rearrangement by polymerase chain reaction (PCR).
  • [MeSH-major] Hemochromatosis / complications. Hemochromatosis / genetics. Leukemia, T-Cell / complications
  • [MeSH-minor] Female. Ferritins / blood. Gene Rearrangement, T-Lymphocyte. Humans. Middle Aged. Phlebotomy. Treatment Outcome


93. Zambello R, Berno T, Cannas G, Baesso I, Binotto G, Bonoldi E, Bevilacqua P, Miorin M, Facco M, Trentin L, Agostini C, Semenzato G: Phenotypic and functional analyses of dendritic cells in patients with lymphoproliferative disease of granular lymphocytes (LDGL). Blood; 2005 Dec 1;106(12):3926-31
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  • [Title] Phenotypic and functional analyses of dendritic cells in patients with lymphoproliferative disease of granular lymphocytes (LDGL).
  • We investigated whether dendritic cells (DCs) play a role in favoring granular lymphocyte (GL) proliferation in patients with lymphoproliferative disease of granular lymphocytes (LDGL).
  • Autologous immature (iDCs) and mature (mDCs) DCs generated in vitro were studied for stimulatory activity on cell proliferation of CD3+ and CD3- GLs.
  • Analysis of BM biopsies demonstrated a topographic distribution of DCs and GLs that indicates contact between the 2 cell types.
  • [MeSH-major] Cell Communication / immunology. Dendritic Cells / metabolism. Granulocytes / metabolism. Lymphoproliferative Disorders / metabolism
  • [MeSH-minor] Antigens, CD3 / metabolism. Cell Proliferation. Flow Cytometry. Humans. Immunohistochemistry. Immunophenotyping. Killer Cells, Natural / immunology. Killer Cells, Natural / metabolism. T-Lymphocytes / immunology. T-Lymphocytes / metabolism

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  • (PMID = 16091452.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antigens, CD3
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94. Yokohama A, Mishra A, Mitsui T, Becknell B, Johns J, Curphey D, Blaser BW, Vandeusen JB, Mao H, Yu J, Caligiuri MA: A novel mouse model for the aggressive variant of NK cell and T cell large granular lymphocyte leukemia. Leuk Res; 2010 Feb;34(2):203-9
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  • [Title] A novel mouse model for the aggressive variant of NK cell and T cell large granular lymphocyte leukemia.
  • Murine models of disease are vital to the understanding of pathogenesis and the development of novel therapeutics.
  • We have previously established interleukin (IL)-15 transgenic (tg) mice that demonstrate rapid proliferation of natural killer (NK) and T cells, followed by spontaneous transformation to lethal leukemia.
  • Herein, we have characterized this model, which has many features in common with the aggressive variants of NK and T large granular lymphocyte leukemia (LGLL) in humans.
  • The LGLL blasts are cytolytic and produce IFN-gammaex vivo.
  • This model should provide opportunities to develop effective standard therapies for this fatal disease.

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  • [Copyright] Copyright 2009 Elsevier Ltd. All rights reserved.
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  • (PMID = 19660811.001).
  • [ISSN] 1873-5835
  • [Journal-full-title] Leukemia research
  • [ISO-abbreviation] Leuk. Res.
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / R01 CA068458; United States / NCI NIH HHS / CA / P01 CA095426-06; United States / NCI NIH HHS / CA / CA016058-30; United States / NCI NIH HHS / CA / P01 CA095426; United States / NCI NIH HHS / CA / P30 CA016058; United States / NCI NIH HHS / CA / CA095426-06; United States / NCI NIH HHS / CA / R37 CA068458; United States / NCI NIH HHS / CA / CA068458-14; United States / NCI NIH HHS / CA / R01 CA068458-14; United States / NCI NIH HHS / CA / P30 CA016058-30
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Interleukin-15; 82115-62-6 / Interferon-gamma
  • [Other-IDs] NLM/ NIHMS130274; NLM/ PMC2814907
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95. Howard MT, Bejanyan N, Maciejewski JP, Hsi ED: T/NK large granular lymphocyte leukemia and coexisting monoclonal B-cell lymphocytosis-like proliferations. An unrecognized and frequent association. Am J Clin Pathol; 2010 Jun;133(6):936-41
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  • [Title] T/NK large granular lymphocyte leukemia and coexisting monoclonal B-cell lymphocytosis-like proliferations. An unrecognized and frequent association.
  • T-cell large granular lymphocyte leukemia (T-LGLL) is a T-cell lymphoproliferative disorder that has recently been associated with B-cell dyscrasias on a spectrum ranging from dysgammaglobulinemia to lymphoma.
  • To investigate the relationship between clonal B-cell and LGLL lymphoproliferations, we systematically studied lymphocytes in 57 patients with T-LGLL or NK lymphocytosis using flow cytometric methods sensitive to low-level B-cell populations.
  • We identified 16 patients (28%) with abnormal B-cell populations; 9 (16%) of the patients had no known history of a B-cell lymphoproliferative disorder.
  • We characterized these abnormal B-cell populations as monoclonal B-cell lymphocytosis and report a high frequency of monoclonal B-cell lymphocytosis in T/NK LGLL.
  • Our findings suggest that certain pathologic factors may operate in patients with T/NK LGLL to drive low-level clonal B-cell proliferations.
  • [MeSH-major] B-Lymphocytes / immunology. Killer Cells, Natural / immunology. Leukemia, Large Granular Lymphocytic / immunology. T-Lymphocytes / immunology
  • [MeSH-minor] Adult. Aged. Female. Flow Cytometry. Humans. Lymphocyte Count. Lymphocytosis / complications. Lymphocytosis / immunology. Lymphocytosis / pathology. Male. Middle Aged. Retrospective Studies

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  • (PMID = 20472852.001).
  • [ISSN] 1943-7722
  • [Journal-full-title] American journal of clinical pathology
  • [ISO-abbreviation] Am. J. Clin. Pathol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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96. Alekshun TJ, Tao J, Sokol L: Aggressive T-cell large granular lymphocyte leukemia: a case report and review of the literature. Am J Hematol; 2007 Jun;82(6):481-5
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  • [Title] Aggressive T-cell large granular lymphocyte leukemia: a case report and review of the literature.
  • The majority of patients with T-cell large granular lymphocyte (LGL) leukemia will have an indolent clinical course.
  • Herein, we report a case of an aggressive T-cell LGL leukemia in a previously healthy 42-year-old Caucasian male who presented with acute onset of B-symptoms, hepatosplenomegaly, lymphocytosis, moderate anemia, and thrombocytopenia.
  • Immunophenotypically, the malignant cells co-expressed CD3(+)CD8(+)CD56(+) markers and the T-cell receptor beta (TCR beta) gene demonstrated clonal rearrangement.
  • A systematic review of all available English literature revealed 12 well-described cases of aggressive T-cell LGL leukemia suggesting that this variant is a new and distinct entity in the spectrum of LGL disorders.
  • [MeSH-major] Leukemia, Large Granular Lymphocytic / diagnosis
  • [MeSH-minor] Adult. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Disease Progression. Follow-Up Studies. Humans. Immunophenotyping. Karyotyping. Male. Remission Induction. Treatment Outcome


97. Oshimi K, Kawa K, Nakamura S, Suzuki R, Suzumiya J, Yamaguchi M, Kameoka J, Tagawa S, Imamura N, Ohshima K, Kojya S, Iwatsuki K, Tokura Y, Sato E, Sugimori H, NK-cell Tumor Study Group: NK-cell neoplasms in Japan. Hematology; 2005 Jun;10(3):237-45
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  • [Title] NK-cell neoplasms in Japan.
  • Neoplasms putatively originating from precursor and mature natural killer (NK) cells are rare, and their clinical features are unclear.
  • A nationwide survey was performed in Japan to clarify the clinical features of these neoplasms diagnosed between 1994 and 1998, and data for 237 patients who met the criteria for putative NK cell-lineage neoplasms were analyzed.
  • Among them, 11 had myeloid/NK-cell precursor acute leukemia, 15 blastic NK-cell lymphoma, 21 precursor NK-cell acute lymphoblastic leukemia, 22 aggressive NK-cell leukemia/lymphoma, 149 nasal-type NK-cell lymphoma (123 nasal and 26 extranasal) and 19 chronic NK lymphocytosis.
  • The median overall survival time of patients with aggressive NK-cell leukemia/lymphoma was 2 months, which for chronic NK lymphocytosis was more than 8 years, and that for the other types of NK-cell neoplasms was between 6 and 22 months.
  • Nasal NK-cell lymphoma and extranasal NK-cell lymphoma share the same histology.
  • The age of affliction was the same, but the sex was different with males predominantly having nasal NK-cell lymphoma and females extranasal NK-cell lymphoma.
  • Patients with extranasal NK-cell lymphoma had the tendency to exhibit a more advanced state of disease, with significantly higher International Prognostic Index and LDH levels, and significantly lower hemoglobin and platelet levels.
  • Precursor NK-cell acute lymphoblastic leukemia and blastic NK-cell lymphoma were arbitrarily defined by the presence or absence of 30% or more of blastic cells in the bone marrow or peripheral blood, but there were no significant differences for affected age, gender, involved sites or prognosis.
  • Aggressive NK-cell leukemia/lymphoma and extranasal NK-cell lymphoma were arbitrarily defined by the presence or absence of 30% or more of large granular lymphocytes in the bone marrow or peripheral blood and it is possible that aggressive NK-cell leukemia/lymphoma is a leukemic phase of extranasal NK-cell lymphoma.
  • The incidence of skin involvement, however, was significantly higher for extranasal NK-cell lymphoma, suggesting that the two diseases are different.
  • In nasal NK-cell lymphoma, Epstein-Barr virus in tumor cells was detected in all patients tested, suggesting its causative role.
  • [MeSH-major] Killer Cells, Natural. Leukemia, Myeloid, Acute / mortality. Lymphoma / mortality. Nasopharyngeal Neoplasms / mortality
  • [MeSH-minor] Disease-Free Survival. Epstein-Barr Virus Infections / mortality. Epstein-Barr Virus Infections / pathology. Female. Herpesvirus 4, Human. Humans. Japan. Male. Survival Analysis


98. Min HS, Hyun CL, Paik JH, Jeon YK, Choi G, Park SH, Seo JW, Kim CW: An autopsy case of aggressive CD30+ extra-nodal NK/T-cell lymphoma initially manifested with granulomatous myositis. Leuk Lymphoma; 2006 Feb;47(2):347-52
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  • [Title] An autopsy case of aggressive CD30+ extra-nodal NK/T-cell lymphoma initially manifested with granulomatous myositis.
  • This study reports an autopsy case of a 53 year-old male with rapidly progressive extra-nodal NK/T-cell lymphoma accompanied with unusual clinical and pathologic features.
  • The biopsy from erythematous skin lesion of trunk showed infiltration of medium sized atypical lymphoid cells with relatively plump cytoplasm and immunophenotype of CD30+, CD56+/- and surface CD3-, which lead to the diagnosis of CD30+ anaplastic large cell lymphoma.
  • After confirmation of EBV infection, he was finally diagnosed as extra-nodal NK/T-cell lymphoma with peculiar immunophenotype of CD3 dim+ and CD30+.
  • This case emphasizes that extra-nodal NK/T-cell lymphoma should be considered as a cause of granulomatous myositis and can express CD30 positivity and CD3 weak positivity, which are unusual but rarely predominant feature of NK/T-cell lymphoma.
  • [MeSH-major] Antigens, CD30 / immunology. Granuloma / pathology. Killer Cells, Natural / pathology. Lymphoma, T-Cell / pathology. Myositis / pathology
  • [MeSH-minor] Antigens, CD3 / immunology. Disease Progression. Fatal Outcome. Humans. Immunophenotyping. Male. Middle Aged

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  • (PMID = 16321870.001).
  • [ISSN] 1042-8194
  • [Journal-full-title] Leukemia & lymphoma
  • [ISO-abbreviation] Leuk. Lymphoma
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antigens, CD3; 0 / Antigens, CD30; 0 / CD3 antigen, zeta chain
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99. Pullarkat VA, Medeiros LJ, Brynes RK: Body cavity-based presentation of natural killer cell lymphoma. Leuk Lymphoma; 2005 Feb;46(2):293-6
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  • [Title] Body cavity-based presentation of natural killer cell lymphoma.
  • We describe an unusual case of a 31-year-old Mexican woman who presented with pleural and peritoneal effusions involved by Epstein-Barr virus-positive non-Hodgkin's lymphoma of natural killer (NK)-cell lineage.
  • Extranodal NK/T-cell lymphoma of nasal type is the current designation for these neoplasms in the recently proposed World Health Organization classification of lymphoid neoplasms.
  • These tumors previously have been referred to many other names, including lethal midline granuloma, midline malignant reticulosis, polymorphic reticulosis, angiocentric immunoproliferative lesion, and angiocentric lymphoma.
  • Nasal-type NK/T-cell lymphomas typically involve the nasal region, but may involve other extranodal sites, such as skin and gastrointestinal tract.
  • The malignant cytologic features and the presence of azurophilic granules within the cell cytoplasm observed in Wright-Giemsa-stained cytocentrifuge preparations led to immunophenotypic and molecular genetic studies that were essential in establishing the correct diagnosis.
  • As demonstrated in the case reported, extranodal NK/T-cell lymphomas of nasal-type can be clinically aggressive and may be associated with paraneoplastic phenomena.
  • [MeSH-major] Killer Cells, Natural / pathology. Lymphoma, T-Cell / pathology. Nose Neoplasms / diagnosis. Pleural Effusion, Malignant / pathology
  • [MeSH-minor] Adult. Diagnosis, Differential. Female. Herpesvirus 4, Human / isolation & purification. Humans. Pleural Cavity / pathology

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  • (PMID = 15621817.001).
  • [ISSN] 1042-8194
  • [Journal-full-title] Leukemia & lymphoma
  • [ISO-abbreviation] Leuk. Lymphoma
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
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100. Makishima H, Ito T, Asano N, Nakazawa H, Shimodaira S, Kamijo Y, Nakazawa Y, Suzuki T, Kobayashi H, Kiyosawa K, Ishida F: Significance of chemokine receptor expression in aggressive NK cell leukemia. Leukemia; 2005 Jul;19(7):1169-74
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  • [Title] Significance of chemokine receptor expression in aggressive NK cell leukemia.
  • Natural killer (NK) cell-type lymphoproliferative diseases of granular lymphocytes can be subdivided into aggressive NK cell leukemia (ANKL) and chronic NK cell lymphocytosis (CNKL).
  • The mechanisms of cell trafficking associated with the chemokine system have been investigated in NK cells.
  • To clarify the mechanism of systemic migration of leukemic NK cells, we enrolled nine ANKL and six CNKL cases, and analyzed the expression profiles and functions of chemokine receptors by flowcytometry and chemotaxis assay.
  • CXCR1 was detected on NK cells in all groups, and CCR5 was positive in all ANKL cells.
  • Proliferating NK cells were simultaneously positive for CXCR1 and CCR5 in all ANKL patients examined, and NK cells with this phenotype did not expand in CNKL patients or healthy donors.
  • These results indicated that the chemokine system might play an important role in the pathophysiology of ANKL and that chemokine receptor profiling might be a novel tool for discriminating ANKL cells from benign NK cells.
  • [MeSH-major] Killer Cells, Natural / pathology. Leukemia, Lymphoid / genetics. Lymphocytosis / genetics. Receptors, Chemokine / genetics
  • [MeSH-minor] Adult. Aged. Biomarkers, Tumor / analysis. Biomarkers, Tumor / genetics. Biomarkers, Tumor / physiology. Cell Movement / drug effects. Cell Movement / physiology. Chemokines / pharmacology. Child. Female. Gene Expression Profiling. Humans. Male. Middle Aged. Phenotype. Receptors, CCR5 / genetics. Receptors, CCR5 / physiology. Receptors, Interleukin-8A / genetics. Receptors, Interleukin-8A / physiology






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