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1. Bonkobara M, Saito T, Yamashita M, Tamura K, Yagihara H, Isotani M, Sato T, Washizu T: Blastic natural killer cell leukaemia in a dog--a case report. Vet J; 2007 Nov;174(3):659-62
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  • [Title] Blastic natural killer cell leukaemia in a dog--a case report.
  • A case of canine non-T, non-B lymphoid leukaemia was determined to be of natural killer (NK) cell lineage by detecting specific expression of canine CD56 mRNA by reverse transcriptase polymerase chain reaction analysis.
  • Although NK cells are usually considered to be morphologically large granular lymphocytes, the malignant NK cells in this case were agranular and blast-like, resembling human blastic NK cell leukaemia.
  • The prognosis of human NK cell leukaemia is usually poor.
  • [MeSH-major] Dog Diseases / diagnosis. Leukemia, Large Granular Lymphocytic / veterinary

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  • (PMID = 17113799.001).
  • [ISSN] 1090-0233
  • [Journal-full-title] Veterinary journal (London, England : 1997)
  • [ISO-abbreviation] Vet. J.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antigens, CD56; 0 / Antineoplastic Agents; 0 / RNA, Messenger; 5J49Q6B70F / Vincristine; 80168379AG / Doxorubicin
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2. Huang Q, Chang KL, Gaal KK, Weiss LM: An aggressive extranodal NK-cell lymphoma arising from indolent NK-cell lymphoproliferative disorder. Am J Surg Pathol; 2005 Nov;29(11):1540-3
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  • [Title] An aggressive extranodal NK-cell lymphoma arising from indolent NK-cell lymphoproliferative disorder.
  • Indolent NK-cell lymphoproliferative disorder, also known as chronic natural killer (NK) cell large granular lymphocytosis (leukemia), is a very rare entity in the World Health Organization (WHO) Classification of Tumors of Hematopoietic & Lymphoid Tissues.
  • Unlike aggressive NK-cell leukemia, which is malignant, the WHO does not specify whether indolent NK-cell lymphoproliferative disorder is reactive or neoplastic.
  • Patients with indolent NK-cell lymphoproliferative disorder are usually asymptomatic older adults who have a nonprogressive, very stable clinical course.
  • We report an unusual case of an aggressive extranodal NK-cell lymphoma, non-nasal type, which presented as a subcutaneous tissue mass, which apparently transformed from a preexisting, untreated indolent NK-cell lymphoproliferative disorder in an 65-year-old otherwise healthy white man.
  • The extranodal NK-cell lymphoma and the NK-cell lymphoproliferative disorder in the blood and bone marrow share a distinctive and identical NK-cell immunophenotype and genotype: CD56/CD8/TIA-1-positive and surface CD3-negative, negative for Epstein-Barr virus infection, and no evidence of T-cell and B-cell receptor gene rearrangements.
  • To the best of our knowledge, such aggressive lymphomatous transformation in an indolent NK-cell lymphoproliferative disorder has not been previously reported.
  • [MeSH-major] Killer Cells, Natural / pathology. Lymphoma, Large B-Cell, Diffuse / pathology. Lymphoproliferative Disorders / complications

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  • (PMID = 16224224.001).
  • [ISSN] 0147-5185
  • [Journal-full-title] The American journal of surgical pathology
  • [ISO-abbreviation] Am. J. Surg. Pathol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 5J49Q6B70F / Vincristine; 80168379AG / Doxorubicin; 8N3DW7272P / Cyclophosphamide; VB0R961HZT / Prednisone; CHOP protocol
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3. Castelli R, Molteni M, Gianelli U, Cro L, Grimoldi MG, Cortelezzi A: Aggressive natural killer cell leukaemia with a complex karyotype: a case report. Ann Hematol; 2006 Jan;85(1):66-8
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  • [Title] Aggressive natural killer cell leukaemia with a complex karyotype: a case report.
  • [MeSH-major] Epstein-Barr Virus Infections / pathology. Killer Cells, Natural / pathology. Leukemia / pathology. Neoplasms, Second Primary / pathology

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  • (PMID = 16184393.001).
  • [ISSN] 0939-5555
  • [Journal-full-title] Annals of hematology
  • [ISO-abbreviation] Ann. Hematol.
  • [Language] eng
  • [Publication-type] Case Reports; Letter
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Anti-Inflammatory Agents; 0 / Antigens, CD; 0 / Antineoplastic Agents, Phytogenic; 0 / Immunosuppressive Agents; 5J49Q6B70F / Vincristine; 8N3DW7272P / Cyclophosphamide; X4W7ZR7023 / Methylprednisolone
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4. Makishima H: [Analysis of chemokine receptor expression in aggressive NK-cell leukemia and chronic NK-cell lymphocytosis]. Rinsho Ketsueki; 2008 Jan;49(1):3-9
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  • [Title] [Analysis of chemokine receptor expression in aggressive NK-cell leukemia and chronic NK-cell lymphocytosis].
  • [MeSH-major] Chemokines / genetics. Chemokines / physiology. Killer Cells, Natural. Leukemia, Lymphoid / genetics. Leukemia, Lymphoid / pathology. Lymphocytosis / genetics. Lymphocytosis / pathology. Receptors, Chemokine / genetics. Receptors, Chemokine / physiology

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  • (PMID = 18277590.001).
  • [ISSN] 0485-1439
  • [Journal-full-title] [Rinshō ketsueki] The Japanese journal of clinical hematology
  • [ISO-abbreviation] Rinsho Ketsueki
  • [Language] jpn
  • [Publication-type] Journal Article; Review
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Chemokines; 0 / Receptors, CCR5; 0 / Receptors, Chemokine; 0 / Receptors, Interleukin-8A
  • [Number-of-references] 20
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5. Greer JP, Mosse CA: Natural killer-cell neoplasms. Curr Hematol Malig Rep; 2009 Oct;4(4):245-52
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  • [Title] Natural killer-cell neoplasms.
  • The natural killer (NK)-cell neoplasms are rare, representing less than 1% of non-Hodgkin lymphoma, except in Asia and Latin America, where they represent 3% to 6%.
  • NK-cell neoplasms include immature acute leukemias; a blastic NK-cell lymphoma, which is obsolete because of its plasmacytoid dendritic-cell origin; and mature NK neoplasms, comprising extranodal NK/T-cell lymphoma (ENKL), nasal-type; aggressive NK-cell leukemia; and chronic NK-cell lymphoproliferative disorders, which are often reactive.
  • Epstein-Barr virus is usually detected in tumor cells of ENKL and aggressive NK-cell leukemia.
  • The latter two mature NK neoplasms are relatively chemoresistant because of the frequent expression of P-glycoprotein.
  • Stem cell transplantation is recommended for advanced disease, owing to a poor prognosis.
  • [MeSH-major] Killer Cells, Natural / pathology. Leukemia / pathology. Lymphoma / pathology. Lymphoproliferative Disorders / pathology
  • [MeSH-minor] Antineoplastic Agents / therapeutic use. Cell Lineage. Cell Transformation, Neoplastic. Humans. Stem Cell Transplantation

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  • (PMID = 20425414.001).
  • [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
  • [Chemical-registry-number] 0 / Antineoplastic Agents
  • [Number-of-references] 42
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6. Lesport E, Baudhuin J, LeMaoult J, Sousa S, Doliger C, Carosella ED, Favier B: Human melanoma cell secreting human leukocyte antigen-G5 inhibit natural killer cell cytotoxicity by impairing lytic granules polarization toward target cell. Hum Immunol; 2009 Dec;70(12):1000-5
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  • [Title] Human melanoma cell secreting human leukocyte antigen-G5 inhibit natural killer cell cytotoxicity by impairing lytic granules polarization toward target cell.
  • The inhibitory role of HLA-G1 on NK cell cytotoxicity is well characterized; however, that of the HLA-G5 isoform secreted by tumor is poorly understood.
  • Our results indicate that the HLA-G5 isoform secreted by M8 melanoma cells is able to protect them from natural killer leukemia cell line (NKL) cytotoxicity.
  • Analysis of NKL/M8-HLA-G5 conjugates by confocal microscopy demonstrates that the inhibition of NKL cytotoxic activity resulted from an impairment of NKL actin reorganization and perforin granules polarization toward M8-HLA-G5 target cell.
  • This study also indicates that HLA-G5 soluble isoform remains evenly distributed in the cytoplasm of M8-HLA-G5 conjugated to NKL cells, suggesting that HLA-G5 does not require to polarize toward effector cell to induce efficient inhibition.
  • These results highlight the inhibitory mechanisms mediated through HLA-G5 leading to tumor escape from NK cell cytotoxicity.
  • [MeSH-major] Cytoplasmic Granules / immunology. HLA Antigens / immunology. Histocompatibility Antigens Class I / immunology. Killer Cells, Natural / immunology. Melanoma / immunology. Skin Neoplasms / immunology. Tumor Escape
  • [MeSH-minor] Actins / immunology. Actins / metabolism. Cell Line, Tumor. Cytotoxicity, Immunologic / immunology. HLA-G Antigens. Humans. Perforin / metabolism. Transfection

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  • (PMID = 19654030.001).
  • [ISSN] 1879-1166
  • [Journal-full-title] Human immunology
  • [ISO-abbreviation] Hum. Immunol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Actins; 0 / HLA Antigens; 0 / HLA-G Antigens; 0 / Histocompatibility Antigens Class I; 126465-35-8 / Perforin
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7. 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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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [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).
  • 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


8. Kishimoto S, Muramatsu M, Gokoh M, Oka S, Waku K, Sugiura T: Endogenous cannabinoid receptor ligand induces the migration of human natural killer cells. J Biochem; 2005 Feb;137(2):217-23
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  • [Title] Endogenous cannabinoid receptor ligand induces the migration of human natural killer cells.
  • In this study, we first examined the effects of 2-arachidonoylglycerol on the motility of human natural killer cells.
  • We found that 2-arachidonoylglycerol induces the migration of KHYG-1 cells (a natural killer leukemia cell line) and human peripheral blood natural killer cells.
  • The migration of natural killer cells induced by 2-arachidonoylglycerol was abolished by treating the cells with SR144528, a CB2 receptor antagonist, suggesting that the CB2 receptor is involved in the 2-arachidonoylglycerol-induced migration.
  • It is conceivable that the endogenous ligand for the cannabinoid receptor, that is, 2-arachidonoylglycerol, affects natural killer cell functions such as migration, thereby contributing to the host-defense mechanism against infectious viruses and tumor cells.
  • [MeSH-major] Arachidonic Acids / physiology. Cell Movement / physiology. Glycerides / physiology. Killer Cells, Natural / immunology. Receptor, Cannabinoid, CB2 / physiology
  • [MeSH-minor] Bornanes / pharmacology. Cell Line. Endocannabinoids. Humans. Ligands. Pyrazoles / pharmacology

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  • (PMID = 15749836.001).
  • [ISSN] 0021-924X
  • [Journal-full-title] Journal of biochemistry
  • [ISO-abbreviation] J. Biochem.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Arachidonic Acids; 0 / Bornanes; 0 / Endocannabinoids; 0 / Glycerides; 0 / Ligands; 0 / Pyrazoles; 0 / Receptor, Cannabinoid, CB2; 0 / SR 144528; 53847-30-6 / 2-arachidonylglycerol
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9. Oshimi K: Progress in understanding and managing natural killer-cell malignancies. Br J Haematol; 2007 Nov;139(4):532-44
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  • [Title] Progress in understanding and managing natural killer-cell malignancies.
  • The World Health Organization classification of haematolymphoid tumours recognizes three categories of natural killer (NK)-cell neoplasms: blastic NK-cell lymphoma, aggressive NK-cell leukaemia, and extranodal NK/T-cell lymphoma, nasal-type.
  • Recent studies indicate that CD4+CD56+ blastic NK-cell lymphoma is of plasmacytoid dendritic cell origin, and true tumours of precursor NK-cell origin may be present mainly in the CD4-CD56+ subset.
  • Myeloid/NK-cell precursor acute leukaemia may also develop from precursor NK cells.
  • However, because the developmental pathway of normal NK cells is not well understood, tumours of precursor NK-cell origin are not clearly identified.
  • Among mature NK-cell tumours, extranodal NK/T-cell lymphoma is relatively common in Asia and Latin America.
  • Aggressive NK-cell leukaemia is rare and has a poor prognosis.
  • Because NK-cell neoplasms are rare and difficult to manage, rigorous studies are required for their understanding and management.
  • [MeSH-major] Killer Cells, Natural / pathology. Leukemia, Lymphoid / therapy
  • [MeSH-minor] Acute Disease. Cell Lineage. Cell Transformation, Neoplastic / pathology. Chronic Disease. Humans. Neoplasm Staging. Preleukemia / pathology. Prognosis

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  • (PMID = 17916099.001).
  • [ISSN] 1365-2141
  • [Journal-full-title] British journal of haematology
  • [ISO-abbreviation] Br. J. Haematol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] England
  • [Number-of-references] 132
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10. 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


11. Suzuki R, Suzumiya J, Yamaguchi M, Nakamura S, Kameoka J, Kojima H, Abe M, Kinoshita T, Yoshino T, Iwatsuki K, Kagami Y, Tsuzuki T, Kurokawa M, Ito K, Kawa K, Oshimi K, NK-cell Tumor Study Group: Prognostic factors for mature natural killer (NK) cell neoplasms: aggressive NK cell leukemia and extranodal NK cell lymphoma, nasal type. Ann Oncol; 2010 May;21(5):1032-40
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Prognostic factors for mature natural killer (NK) cell neoplasms: aggressive NK cell leukemia and extranodal NK cell lymphoma, nasal type.
  • BACKGROUND: Patients with natural killer (NK) cell neoplasms, aggressive NK cell leukemia (ANKL) and extranodal NK cell lymphoma, nasal type (ENKL), have poor outcome.
  • The purpose of this study is to draw a prognostic model of total NK cell neoplasms.
  • Using these four variables, an NK prognostic index was successfully constructed.
  • CONCLUSION: The current prognostic model successfully stratified patients with NK cell neoplasms with different outcomes.


12. Ham MF, Ko YH: Natural killer cell neoplasm: biology and pathology. Int J Hematol; 2010 Dec;92(5):681-9
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Natural killer cell neoplasm: biology and pathology.
  • Natural killer (NK) cell neoplasm is a heterogeneous disease group.
  • In the latest World Health Organization (WHO) classification of tumours of hematopoietic and lymphoid tissues (2008), disease entities considered as NK-cell derivation include NK-lymphoblastic leukemia/lymphoma, chronic lymphoproliferative disorders of NK cells, aggressive NK-cell leukemia, and extranodal NK-cell lymphoma, nasal-type.
  • Despite recent advances in NK-cell research, which have expanded our understanding of the biology of NK-cell neoplasm, it cannot yet be sharply delineated from myeloid neoplasms and T-cell neoplasms even in some "well-known" entity, such as extranodal NK/T-cell lymphoma.
  • This review describes current knowledge of the biology of NK cells and pathology of NK neoplasms as classified in the 2008 WHO classification of tumours of hematopoietic and lymphoid tissues.
  • [MeSH-major] Killer Cells, Natural / pathology. Neoplasms / pathology
  • [MeSH-minor] Humans. Lymphoma, Extranodal NK-T-Cell / pathology. Lymphoproliferative Disorders / pathology. Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology

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  • (PMID = 21132576.001).
  • [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; Review
  • [Publication-country] Japan
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13. Sugimoto K, Oshimi K: [Treatment of chronic lymphocytic leukemia and NK-cell leukemia/lymphoma]. Nihon Rinsho; 2007 Jan 28;65 Suppl 1:569-74
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] [Treatment of chronic lymphocytic leukemia and NK-cell leukemia/lymphoma].
  • [MeSH-major] Leukemia, Lymphocytic, Chronic, B-Cell / therapy. Leukemia, T-Cell / therapy. Lymphoma, T-Cell / therapy
  • [MeSH-minor] Humans. Killer Cells, Natural

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  • (PMID = 17476757.001).
  • [ISSN] 0047-1852
  • [Journal-full-title] Nihon rinsho. Japanese journal of clinical medicine
  • [ISO-abbreviation] Nippon Rinsho
  • [Language] jpn
  • [Publication-type] Journal Article; Review
  • [Publication-country] Japan
  • [Number-of-references] 18
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14. 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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15. Schellekens J, Tilanus MG, Rozemuller EH: The elucidation of KIR2DL4 gene polymorphism. Mol Immunol; 2008 Apr;45(7):1900-6
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  • The killer cell immunoglobulin-like receptors (KIRs) on NK cells recognize defined groups of HLA class I alleles.
  • By this mechanism the NK cells fulfil a significant role in the first line of defense against infectious agents and cancer.
  • For the treatment of leukaemia this NK cell allorecognition is of great importance.

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  • (PMID = 18082267.001).
  • [ISSN] 0161-5890
  • [Journal-full-title] Molecular immunology
  • [ISO-abbreviation] Mol. Immunol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / DNA, Complementary; 0 / KIR2DL4 protein, human; 0 / Receptors, KIR2DL4
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16. Zhang K, Prichard JW, Brown RE: Blastic natural killer (NK) cell leukemia (agranular CD4+CD56+ leukemia). Ann Clin Lab Sci; 2006;36(2):212-5
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  • [Title] Blastic natural killer (NK) cell leukemia (agranular CD4+CD56+ leukemia).
  • Blastic NK cell lymphoma is a rare hematolymphoid neoplasm.
  • This report illustrates an unusual presentation of this entity, namely as a primary leukemia, but without skin lesions.
  • [MeSH-major] Bone Marrow Neoplasms / diagnosis. Killer Cells, Natural. Leukemia, Lymphoid / diagnosis. Precursor Cell Lymphoblastic Leukemia-Lymphoma / diagnosis

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  • (PMID = 16682521.001).
  • [ISSN] 0091-7370
  • [Journal-full-title] Annals of clinical and laboratory science
  • [ISO-abbreviation] Ann. Clin. Lab. Sci.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antigens, CD4; 0 / Antigens, CD56
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17. Matano S, Terahata S, Nakamura S, Kobayashi K, Sugimoto T: CD56-positive acute lymphoblastic leukemia. Acta Haematol; 2005;114(3):160-3
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  • [Title] CD56-positive acute lymphoblastic leukemia.
  • We report a patient with lung cancer who developed CD56-positive acute lymphoblastic leukemia.
  • There were no rearrangements of T-cell receptor (TCR)-beta, TCR-gamma, or immunoglobulin heavy chain.
  • Systemic examination did not detect any tumors other than pulmonary adenocarcinoma, and the patient was diagnosed as having acute natural killer (NK) cell leukemia.
  • The course of the disease was complicated by a lung abscess, and the patient died 3 months after the diagnosis.
  • We considered that the diagnosis was blastic NK cell lymphoma/leukemia subtype.
  • However, it actually was myeloid/NK cell precursor leukemia subtype that weakly expressed CD13.
  • [MeSH-major] Antigens, CD56 / metabolism. Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • [MeSH-minor] Aged. Humans. Immunophenotyping. Killer Cells, Natural / classification. Killer Cells, Natural / immunology. Killer Cells, Natural / pathology. Male

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  • [Copyright] (c) 2005 S. Karger AG, Basel
  • (PMID = 16227680.001).
  • [ISSN] 0001-5792
  • [Journal-full-title] Acta haematologica
  • [ISO-abbreviation] Acta Haematol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Switzerland
  • [Chemical-registry-number] 0 / Antigens, CD56
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18. Oka K, Nagayama R, Mori N: Epstein-Barr virus-associated proliferative disorder presenting as Hodgkin's lymphoma and developing as aggressive natural killer-cell leukemia 19 years later: a case report of composite lymphoma. Pathol Res Pract; 2009;205(10):730-4
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  • [Title] Epstein-Barr virus-associated proliferative disorder presenting as Hodgkin's lymphoma and developing as aggressive natural killer-cell leukemia 19 years later: a case report of composite lymphoma.
  • We describe a patient who was diagnosed as having classic Hodgkin's lymphoma at 29 years of age, and aggressive natural killer-cell leukemia at 48 years.
  • Hodgkin and Reed-Sternberg cells in the lymph node expressed CD30, CD15, T-cell intracellular antigen-1 (TIA-1), perforin, granzyme B, and Epstein-Barr virus-encoded RNA (EBER).
  • Natural killer-cell leukemia cells in the bone marrow expressed cytoplasmic CD3epsilon, TIA-1, perforin, granzyme B, and EBER, and some neoplastic cells expressed CD56 (123C3).
  • Fluorescence-activated cell sorter (FACS) analysis showed that neoplastic cells expressed CD56.
  • Neither a rearrangement band of the T-cell receptor gene nor that of the immunoglobulin heavy chain gene was detected.
  • [MeSH-major] Epstein-Barr Virus Infections / complications. Hodgkin Disease / pathology. Leukemia, Large Granular Lymphocytic / pathology. Neoplasms, Second Primary / pathology

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  • (PMID = 19269751.001).
  • [ISSN] 1618-0631
  • [Journal-full-title] Pathology, research and practice
  • [ISO-abbreviation] Pathol. Res. Pract.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Germany
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19. Osuji N, Del Giudice I, Matutes E, Morilla A, Owusu-Ankomah K, Morilla R, Dunlop A, Catovksy D: CD52 expression in T-cell large granular lymphocyte leukemia--implications for treatment with alemtuzumab. Leuk Lymphoma; 2005 May;46(5):723-7
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  • [Title] CD52 expression in T-cell large granular lymphocyte leukemia--implications for treatment with alemtuzumab.
  • Few reports on the successful treatment of T-cell large granular lymphocyte (LGL) leukemia with the humanized anti-CD52 monoclonal antibody alemtuzumab are emerging in the literature.
  • Using semi-quantitative 2- and 3-color flow cytometry, we documented the expression of CD52 in 100% of abnormal cells in T-cell LGL leukemia (n = 11) and natural killer (NK) cell LGL leukemia (n = 2), and showed no significant difference in CD52 expression between T-cell prolymphocytic leukemia (PLL) and T-cell LGL leukemia.
  • Higher CD52 expression has been noted in responders to alemtuzumab in T-cell PLL and in chronic lymphocytic leukemia (CLL), a B-cell disorder.
  • The strong and consistent expression of CD52 shown here highlights the potential role of alemtuzumab in the treatment of refractory T-cell LGL leukemia and possibly aggressive NK cell leukemia.
  • [MeSH-major] Antibodies, Monoclonal / therapeutic use. Antibodies, Neoplasm / therapeutic use. Antigens, CD / biosynthesis. Antigens, Neoplasm / biosynthesis. Antineoplastic Agents / therapeutic use. Glycoproteins / biosynthesis. Leukemia, Lymphoid / drug therapy. Leukemia, Lymphoid / immunology. Leukemia, T-Cell / drug therapy

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  • (PMID = 16019510.001).
  • [ISSN] 1042-8194
  • [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 / Antigens, CD; 0 / Antigens, Neoplasm; 0 / Antineoplastic Agents; 0 / CD52 antigen; 0 / Glycoproteins; 3A189DH42V / alemtuzumab
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20. Shen L, Au WY, Guo T, Wong KY, Wong ML, Tsuchiyama J, Yuen PW, Kwong YL, Liang RH, Srivastava G: Proteasome inhibitor bortezomib-induced apoptosis in natural killer (NK)-cell leukemia and lymphoma: an in vitro and in vivo preclinical evaluation. Blood; 2007 Jul 1;110(1):469-70
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  • [Title] Proteasome inhibitor bortezomib-induced apoptosis in natural killer (NK)-cell leukemia and lymphoma: an in vitro and in vivo preclinical evaluation.
  • [MeSH-major] Boronic Acids / therapeutic use. Killer Cells, Natural / pathology. Leukemia, T-Cell / drug therapy. Lymphoma, T-Cell / drug therapy. Pyrazines / therapeutic use
  • [MeSH-minor] Apoptosis / drug effects. Bortezomib. Cell Line, Tumor. Drug Screening Assays, Antitumor. Humans. Protease Inhibitors / therapeutic use. Tumor Cells, Cultured

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  • (PMID = 17579189.001).
  • [ISSN] 0006-4971
  • [Journal-full-title] Blood
  • [ISO-abbreviation] Blood
  • [Language] eng
  • [Publication-type] Letter; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Boronic Acids; 0 / Protease Inhibitors; 0 / Pyrazines; 69G8BD63PP / Bortezomib
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21. Jeon YK, Park CH, Kim KY, Li YC, Kim J, Kim YA, Paik JH, Park BK, Kim CW, Kim YN: The heat-shock protein 90 inhibitor, geldanamycin, induces apoptotic cell death in Epstein-Barr virus-positive NK/T-cell lymphoma by Akt down-regulation. J Pathol; 2007 Oct;213(2):170-9
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  • [Title] The heat-shock protein 90 inhibitor, geldanamycin, induces apoptotic cell death in Epstein-Barr virus-positive NK/T-cell lymphoma by Akt down-regulation.
  • NK/T-cell lymphoma (NKTL) is strongly associated with latent Epstein-Barr virus (EBV) infection.
  • Recently, latent membrane protein 1 (LMP1), an EBV oncoprotein, was reported to activate the phosphatidylinositol-3 kinase (PI3K)/Akt pathway for cell survival.
  • Because geldanamycin (GA) and its derivative, 17-allylamino-17-demethoxygeldanamycin (17-AAG), exhibit anti-tumour activity by degrading HSP90 client proteins, including Akt, we investigated the effect of GA and 17-AAG on the survival of NKTL cell lines.
  • EBV-positive NKTL cell lines, Hank-1 and NK-YS, and an EBV-negative NK leukaemia cell line, NK-L, were treated with PI3K and Akt inhibitors, GA, and 17-AAG, and were subjected to apoptosis and cell viability assays, and immunoblot analysis.
  • EBV-positive B-lymphoblastoid cell lines IM9 and LMP1-transfected IM9 (IM9-LMP1) were also included.
  • Hank-1 and NK-YS cell viability was compromised and apoptosis was induced by LY294002 (PI3K inhibitor) or Akt inhibitor II.
  • The intrinsic level of pAkt was higher in EBV-positive NKTL cells than in EBV-negative NK-L, and GA or 17-AAG decreased the viability of NKTL cells more efficiently than NK-L.
  • Importantly, GA showed little effect on the viability of normal peripheral NK cells as non-neoplastic counterparts for comparison.
  • [MeSH-major] Antibiotics, Antineoplastic / pharmacology. Apoptosis / drug effects. Benzoquinones / pharmacology. HSP90 Heat-Shock Proteins / antagonists & inhibitors. Herpesvirus 4, Human / isolation & purification. Lactams, Macrocyclic / pharmacology. Lymphoma, Extranodal NK-T-Cell / pathology
  • [MeSH-minor] Cell Survival. Down-Regulation / drug effects. Drug Evaluation, Preclinical. Humans. Lymphoma, B-Cell / metabolism. Lymphoma, B-Cell / pathology. Lymphoma, B-Cell / virology. Membrane Potential, Mitochondrial / physiology. Oncogene Protein v-akt / metabolism. Phosphatidylinositol 3-Kinases / metabolism. Signal Transduction. Tumor Cells, Cultured

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  • (PMID = 17768706.001).
  • [ISSN] 0022-3417
  • [Journal-full-title] The Journal of pathology
  • [ISO-abbreviation] J. Pathol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antibiotics, Antineoplastic; 0 / Benzoquinones; 0 / HSP90 Heat-Shock Proteins; 0 / Lactams, Macrocyclic; 4GY0AVT3L4 / tanespimycin; EC 2.7.1.- / Phosphatidylinositol 3-Kinases; EC 2.7.11.1 / Oncogene Protein v-akt; Z3K3VJ16KU / geldanamycin
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22. Slater DN: The new World Health Organization-European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas: a practical marriage of two giants. Br J Dermatol; 2005 Nov;153(5):874-80
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  • The new classification will facilitate more uniformity in diagnosis, management and treatment of cutaneous lymphomas.
  • In particular, it provides a useful distinction between indolent and more aggressive types of primary cutaneous lymphoma and provides practical advice on preferred management and treatment regimens.
  • In cutaneous T-cell lymphomas, these include folliculotropic mycosis fungoides, defining features of Sézary syndrome, primary cutaneous CD30+ lymphoproliferative disorders (primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis and borderline lesions) and subcutaneous panniculitis-like T-cell lymphoma.
  • Primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoma, primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma and cutaneous gamma/delta T-cell lymphoma are allocated provisional entry status and thereby afford better definitions for some cases of currently unspecified primary cutaneous peripheral T-cell lymphoma.
  • In cutaneous B-cell lymphomas, diseases which have found new consensus agreement include primary cutaneous marginal zone B-cell lymphoma, primary cutaneous follicular centre lymphoma, primary cutaneous diffuse large B-cell lymphoma, leg type and primary cutaneous diffuse large B-cell lymphoma, other.
  • CD4+/CD56+ haematodermic neoplasm (early plasmacytoid dendritic cell leukaemia/lymphoma) now appears as a precursor haematological neoplasm and replaces the previous terminology of blastic NK-cell lymphoma.
  • The new classification raises interesting new problems and questions about primary cutaneous lymphoma and some of these are discussed in this article.
  • It is, however, a splendid signpost indicating the direction in which research in cutaneous lymphoma needs to go.
  • [MeSH-major] Lymphoma / classification. Skin Neoplasms / classification
  • [MeSH-minor] Humans. Killer Cells, Natural. Lymphoma, B-Cell / classification. Lymphoma, T-Cell, Cutaneous / classification. Mycosis Fungoides / classification. Sezary Syndrome / classification. World Health Organization

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  • (PMID = 16225594.001).
  • [ISSN] 0007-0963
  • [Journal-full-title] The British journal of dermatology
  • [ISO-abbreviation] Br. J. Dermatol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Number-of-references] 23
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23. Gross SA, Zhu X, Bao L, Ryder J, Le A, Chen Y, Wang XQ, Irons RD: A prospective study of 728 cases of non-Hodgkin lymphoma from a single laboratory in Shanghai, China. Int J Hematol; 2008 Sep;88(2):165-73
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  • [Title] A prospective study of 728 cases of non-Hodgkin lymphoma from a single laboratory in Shanghai, China.
  • Diagnosis and classification was established in a single laboratory according to the 2001 WHO classification system.
  • The frequency of non-Hodgkin lymphoma was 87.6% (n = 728) and Hodgkin lymphoma was 12.4% (n = 103).
  • The most prevalent NHL subtypes diagnosed using WHO criteria were diffuse large B cell lymphoma (DLBCL), precursor B lymphoblastic leukemia/lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).
  • Although a low incidence has been reported in some Asian populations, CLL/SLL was commonly encountered, indicating that chronic lymphoid neoplasms are not rare in Shanghai.
  • Consistent with previous reports, our findings indicate a decrease in the frequency of follicular lymphoma and an increase in T cell neoplasms compared to the West.
  • Precursor T lymphoblastic leukemia/lymphoma, anaplastic large T cell lymphoma, aggressive NK cell leukemia, angioimmunoblastic T cell lymphoma and peripheral T cell lymphoma were prominent subtypes of T cell NHL.
  • [MeSH-major] Asian Continental Ancestry Group / statistics & numerical data. Lymphoma, Non-Hodgkin / classification. Lymphoma, Non-Hodgkin / ethnology

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  • (PMID = 18648906.001).
  • [ISSN] 0925-5710
  • [Journal-full-title] International journal of hematology
  • [ISO-abbreviation] Int. J. Hematol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / DNA, Neoplasm
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24. Lee AJ, Kim SG, Jeon CH, Suh HS, Yoon GS, Seo AN: A case of natural killer cell leukemia misdiagnosed as tuberculous lymphadenopathy. Korean J Lab Med; 2009 Jun;29(3):194-8
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  • [Title] A case of natural killer cell leukemia misdiagnosed as tuberculous lymphadenopathy.
  • Natural killer (NK) cell neoplasms are a group of rare but highly malignant tumors.
  • We report here one case of NK cell leukemia.
  • Because of the absence of the markers of T-cell, B-cell, and myeloid lineage-specific antigens, we added CD16/56 for the immunophenotyping and the blasts were positive (94%).
  • The tumor cells of biopsied lymph node were only positive for CD56, consistent with NK cell lymphoma.
  • Thus this patient was diagnosed with blastic NK cell lymphoma/leukemia involving bone marrow and lymph node.
  • [MeSH-major] Killer Cells, Natural / pathology. Leukemia / diagnosis
  • [MeSH-minor] Antigens, CD45 / metabolism. Bone Marrow / pathology. Female. HLA-DR Antigens / metabolism. Humans. Middle Aged. Tuberculosis, Lymph Node / diagnosis

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  • (PMID = 19571615.001).
  • [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 / HLA-DR Antigens; EC 3.1.3.48 / Antigens, CD45
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25. Yonescu R, Hristov AC, Ahmad A, Overby A, Thomas GH, Griffin CA: Cytogenetic characterization of natural killer cell leukemia. Cancer Genet Cytogenet; 2008 Jun;183(2):125-30
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  • [Title] Cytogenetic characterization of natural killer cell leukemia.
  • Natural killer (NK) cell neoplasms are rare neoplasms characterized by cells with NK characteristics.
  • Karyotype of the unstimulated peripheral blood at diagnosis was 46,XX,i(7)(q10),der(17)t(1;17)(q21;p11.1),-18,+mar[15].
  • Notably, a single cell with only an i(7q) was found, suggesting that this was the primary chromosomal abnormality in the neoplasm.
  • The abnormalities seen in chromosomes 7 and 17 are consistent with previous reports of chromosomal abnormalities in NK-cell lymphomas.
  • [MeSH-major] Chromosome Aberrations. Killer Cells, Natural / immunology. Leukemia / genetics

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  • [Copyright] (c) 2008 Elsevier Inc.
  • (PMID = 18503833.001).
  • [ISSN] 1873-4456
  • [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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26. Nakashima Y, Tagawa H, Suzuki R, Karnan S, Karube K, Ohshima K, Muta K, Nawata H, Morishima Y, Nakamura S, Seto M: Genome-wide array-based comparative genomic hybridization of natural killer cell lymphoma/leukemia: different genomic alteration patterns of aggressive NK-cell leukemia and extranodal Nk/T-cell lymphoma, nasal type. Genes Chromosomes Cancer; 2005 Nov;44(3):247-55
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  • [Title] Genome-wide array-based comparative genomic hybridization of natural killer cell lymphoma/leukemia: different genomic alteration patterns of aggressive NK-cell leukemia and extranodal Nk/T-cell lymphoma, nasal type.
  • Natural killer (NK) cell lymphomas/leukemias are highly aggressive lymphoid malignancies, but little is known about their genomic alterations, and thus there is an urgent need for identification and analysis of NK cell lymphomas/leukemias.
  • We performed an array CGH analysis for 27 NK-cell lymphoma/leukemia cases that were classified into two disease groups based on the World Health Organization Classification (10 aggressive NK-cell leukemia cases and 17 extranodal NK/T-cell [NK/T] lymphomas, nasal type).
  • The recurrent regions characteristic of the aggressive NK-cell leukemia group compared with those of the extranodal NK/T lymphoma, nasal-type group, were gain of 1q and loss of 7p15.1-p22.3 and 17p13.1.
  • Recurrent regions characteristic of the extranodal NK/T lymphoma, nasal-type group, compared with those of the other group were gain of 2q, and loss of 6q16.1-q27, 11q22.3-q23.3, 5p14.1-p14.3, 5q34-q35.3, 1p36.23-p36.33, 2p16.1-p16.3, 4q12, and 4q31.3-q32.1.
  • Our results can be expected to provide further insights into the genetic basis of lymphomagenesis and the clinicopathologic features of NK-cell lymphomas/leukemias.
  • [MeSH-major] Chromosome Aberrations. Chromosomes, Human / genetics. Genome, Human. Killer Cells, Natural / pathology. Leukemia, T-Cell / genetics. Lymphoma, T-Cell / genetics. Nose Neoplasms / genetics


27. 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.
  • 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.
  • 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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28. Ando M, Sugimoto K, Kitoh T, Sasaki M, Mukai K, Ando J, Egashira M, Schuster SM, Oshimi K: Selective apoptosis of natural killer-cell tumours by l-asparaginase. Br J Haematol; 2005 Sep;130(6):860-8
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  • [Title] Selective apoptosis of natural killer-cell tumours by l-asparaginase.
  • We examined the effectiveness of various anti-tumour agents to natural killer (NK)-cell tumour cell lines and samples, which are generally resistant to chemotherapy, using flow cytometric terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labelling (TUNEL) assay.
  • Although NK-YS and NK-92 were highly resistant to various anti-tumour agents, l-asparaginase induced apoptosis in these two NK-cell lines.
  • NK-cell leukaemia/lymphoma and acute lymphoblastic leukaemia (ALL) samples were selectively sensitive to l-asparaginase and to doxorubicin (DXR) respectively.
  • Samples of chronic NK lymphocytosis, an NK-cell disorder with an indolent clinical course, were resistant to both drugs.
  • Our study clearly separated two major categories of NK-cell disorders and ALL according to the sensitivity to DXR and l-asparaginase.
  • At least in nasal-type NK-cell lymphoma, there was a good correlation among asparagine synthetase expression, in vitro sensitivity and clinical response to l-asparaginase.
  • In aggressive NK-cell leukaemia, although asparagine synthetase expression was high at both mRNA and protein levels, l-asparaginase induced considerable apoptosis.
  • We confirmed rather specific anti-tumour activity of l-asparaginase against NK-cell tumours in vitro, which provides an experimental background to the clinical use of l-asparaginase for NK-cell tumours.
  • [MeSH-major] Antineoplastic Agents / pharmacology. Apoptosis / drug effects. Asparaginase / pharmacology. Killer Cells, Natural. Leukemia, T-Cell / pathology. Lymphoma, T-Cell / pathology
  • [MeSH-minor] Aspartate-Ammonia Ligase / biosynthesis. Aspartate-Ammonia Ligase / genetics. Cell Line, Tumor. Doxorubicin / pharmacology. Drug Resistance, Neoplasm. Humans. In Situ Nick-End Labeling. Lymphocytosis / pathology. RNA, Messenger / genetics. RNA, Neoplasm / genetics

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  • (PMID = 16156856.001).
  • [ISSN] 0007-1048
  • [Journal-full-title] British journal of haematology
  • [ISO-abbreviation] Br. J. Haematol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / RNA, Messenger; 0 / RNA, Neoplasm; 80168379AG / Doxorubicin; EC 3.5.1.1 / Asparaginase; EC 6.3.1.1 / Aspartate-Ammonia Ligase
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29. Osuji N, Matutes E, Morilla A, Del Giudice I, Wotherspoon A, Catovsky D: Prolonged treatment response in aggressive natural killer cell leukemia. Leuk Lymphoma; 2005 May;46(5):757-63
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  • [Title] Prolonged treatment response in aggressive natural killer cell leukemia.
  • We describe a case of natural killer (NK) cell leukemia with acute presentation, systemic symptoms and hepatosplenomegaly.
  • The uniform and aberrant phenotype of NK cells with infiltration of bone marrow and spleen was in keeping with a malignant diagnosis.
  • Aggressive presentation was demonstrated by marked constitutional symptoms and significant tumor burden (liver, spleen, blood, bone marrow).
  • We discuss the difficulties in the diagnosis of this condition, explore possible causes of cytopenia(s), and highlight the role of immunosuppression in controlling disease manifestations in large granular lymphocyte proliferative disorders.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Killer Cells, Natural / pathology. Leukemia / therapy

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  • (PMID = 16019515.001).
  • [ISSN] 1042-8194
  • [Journal-full-title] Leukemia & lymphoma
  • [ISO-abbreviation] Leuk. Lymphoma
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Recombinant Proteins; 11096-26-7 / Erythropoietin; 395575MZO7 / Pentostatin; 83HN0GTJ6D / Cyclosporine
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30. Chee LC, Fahey V, Juneja S, Lieschke GJ, Szer J: Images in haematology. Relapsed blastic natural killer cell leukaemia with splenic rupture. Br J Haematol; 2006 Oct;135(1):2
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  • [Title] Images in haematology. Relapsed blastic natural killer cell leukaemia with splenic rupture.
  • [MeSH-major] Killer Cells, Natural. Lymphoma, T-Cell / complications. Splenic Rupture / etiology

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  • (PMID = 16848796.001).
  • [ISSN] 0007-1048
  • [Journal-full-title] British journal of haematology
  • [ISO-abbreviation] Br. J. Haematol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
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31. 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

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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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32. Armor JF, Fazili J, Toubia N, Kern W, Kamble R, Kharfan-Dabaja MA: Remission of natural-killer cell lymphoma of the liver with anti-hepatitis C therapy. Am J Hematol; 2005 Mar;78(3):212-5
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  • [Title] Remission of natural-killer cell lymphoma of the liver with anti-hepatitis C therapy.
  • A rare subtype of malignancy arising from cells of putative natural killer (NK) origin is being recognized as a distinct clinicopathological entity.
  • Viruses including hepatitis C have been reported in association with various types of NHL but not the NK-cell subtype.
  • We hereby report a unique case of a patient with hepatitis C who developed hepatic NK-cell lymphoma and chronic NK-cell leukemia.
  • [MeSH-major] Antiviral Agents / therapeutic use. Hepatitis C / drug therapy. Killer Cells, Natural / pathology. Liver Neoplasms / pathology. Lymphoma, Non-Hodgkin / pathology. Tumor Virus Infections / pathology

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  • (PMID = 15726605.001).
  • [ISSN] 0361-8609
  • [Journal-full-title] American journal of hematology
  • [ISO-abbreviation] Am. J. Hematol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antiviral Agents; 0 / Interferon-alpha; 0 / Recombinant Proteins; 49717AWG6K / Ribavirin; 99210-65-8 / interferon alfa-2b
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33. 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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34. Murashige N, Kami M, Kishi Y, Kim SW, Takeuchi M, Matsue K, Kanda Y, Hirokawa M, Kawabata Y, Matsumura T, Kusumi E, Hirabayashi N, Nagafuji K, Suzuki R, Takeuchi K, Oshimi K: Allogeneic haematopoietic stem cell transplantation as a promising treatment for natural killer-cell neoplasms. Br J Haematol; 2005 Aug;130(4):561-7
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  • [Title] Allogeneic haematopoietic stem cell transplantation as a promising treatment for natural killer-cell neoplasms.
  • The efficacy of allogeneic haematopoietic stem-cell transplantation (allo-HSCT) for natural killer (NK)-cell neoplasms is unknown.
  • We investigated the results of allo-HSCT for NK-cell neoplasms between 1990 and 2003 through questionnaires.
  • After reclassification by a haematopathologist, of 345 patients who underwent allo-HSCT for malignant lymphoma, 28 had NK-cell neoplasms (World Health Organization classification): extranodal NK/T-cell lymphoma (n=22), blastic NK-cell lymphoma (n=3), and aggressive NK-cell leukaemia (n=3).
  • Stem-cell source was bone marrow in eight and mobilised peripheral blood in 20.
  • In multivariate analysis, stem cell source (BM versus peripheral blood; relative risk 3.03), age (>or=40 years vs. <40 years; relative risk 2.85), and diagnoses (extranodal NK/T-cell lymphoma versus others; relative risk 3.94) significantly affected PFS.
  • Allo-HSCT is a promising treatment for NK-cell neoplasms.
  • [MeSH-major] Hematopoietic Stem Cell Transplantation. Killer Cells, Natural / immunology. Lymphoma, T-Cell / immunology
  • [MeSH-minor] Adult. Bone Marrow Transplantation. Disease-Free Survival. Female. Follow-Up Studies. Graft vs Host Disease. Humans. Male. Middle Aged. Peripheral Blood Stem Cell Transplantation. Proportional Hazards Models. Risk. Transplantation, Homologous

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  • (PMID = 16098071.001).
  • [ISSN] 0007-1048
  • [Journal-full-title] British journal of haematology
  • [ISO-abbreviation] Br. J. Haematol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
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35. 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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36. Nikolova M, Guenova M, Taskov H, Marie-Cardine A, Boumsell L, Bensussan A: SC3 monoclonal antibody defines a novel specific human B-cell surface antigen differentially expressed on B-cell leukaemias and lymphomas and involved in the proliferation of normal and malignant B lymphocytes. Cell Immunol; 2005 Jul-Aug;236(1-2):92-100
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  • [Title] SC3 monoclonal antibody defines a novel specific human B-cell surface antigen differentially expressed on B-cell leukaemias and lymphomas and involved in the proliferation of normal and malignant B lymphocytes.
  • The monoclonal antibody SC3 was raised against the NK leukaemia cell line YTindi.
  • It detected a 98-kDa surface antigen with weak expression on a restricted number of leukaemia cell lines under reducing conditions.
  • SC3 mAb labelled 5-10% of normal peripheral blood lymphocytes corresponding almost exclusively to B lymphocytes, and 60-70% of tonsillar B cells.
  • Practically, all B-CLL studied expressed SC3 mAb reactive epitope although with variable intensity, while MCL and PLL were negative.
  • This effect was much weaker with B-CLL cells but was increased after cross-linking with an anti-IgM antibody.
  • The restricted expression pattern combined with molecular weight and functional data indicate that SC3 mAb may detect a novel B-cell antigen mostly expressed by early and naive B cells.
  • Although its expression in B-cell malignancies was not limited to a single differentiation stage, it might confer specific functional characteristics to the positive malignant cells.
  • [MeSH-major] Antigens, Differentiation, B-Lymphocyte / immunology. Antigens, Surface / immunology. B-Lymphocytes / immunology. Leukemia, B-Cell / immunology. Lymphoma, B-Cell / immunology

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  • (PMID = 16197933.001).
  • [ISSN] 0008-8749
  • [Journal-full-title] Cellular immunology
  • [ISO-abbreviation] Cell. Immunol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antigens, Differentiation, B-Lymphocyte; 0 / Antigens, Surface; 0 / Epitopes, B-Lymphocyte
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37. 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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38. 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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39. Ino K, Masuya M, Nakamori Y, Suzuki K, Mizutani M, Sekine T, Yamaguchi M, Nakase K, Kaida K, Ogawa H, Katayama N: [Aggressive NK-cell leukemia with sustained relapse-free survival after allogeneic peripheral blood stem cell transplantation]. Rinsho Ketsueki; 2010 Apr;51(4):258-63
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  • [Title] [Aggressive NK-cell leukemia with sustained relapse-free survival after allogeneic peripheral blood stem cell transplantation].
  • A bone marrow examination showed several hemophagocytic macrophages, and a diagnosis of hemophagocytic syndrome was made.
  • A repeat bone marrow examination demonstrated that 28.4% of marrow nucleated cells were atypical lymphocytes, which were positive for CD2, CD7, CD16, CD56, and HLA-DR.
  • Clonality of these proliferating NK cells was confirmed by an analysis of EB virus terminal repeat sequence and cytogenetic analysis, and final diagnosis of aggressive NK-cell leukemia was made.
  • He received allogeneic peripheral blood stem cell transplantation from his one locus mismatched son, and is alive with no evidence of disease 20 months after transplantation.
  • [MeSH-major] Killer Cells, Natural. Leukemia, Lymphoid / therapy. Peripheral Blood Stem Cell Transplantation


40. Ito T, Makishima H, Nakazawa H, Kobayashi H, Shimodaira S, Nakazawa Y, Kitano K, Matsuda K, Hidaka E, Ishida F: Promising approach for aggressive NK cell leukaemia with allogeneic haematopoietic cell transplantation. Eur J Haematol; 2008 Aug;81(2):107-11
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  • [Title] Promising approach for aggressive NK cell leukaemia with allogeneic haematopoietic cell transplantation.
  • OBJECTIVES: Aggressive natural killer cell leukaemia (ANKL) is a malignant disorder of mature NK cells with a poor prognosis, for which no effective therapeutic approach has been established.
  • We investigated the role of allogeneic haematopoietic cell transplantion (allo-HCT) in ANKL.
  • [MeSH-major] Hematopoietic Stem Cell Transplantation / methods. Killer Cells, Natural. Leukemia, Lymphoid / therapy
  • [MeSH-minor] Adult. Bone Marrow Transplantation. Cord Blood Stem Cell Transplantation. Female. Herpesvirus 4, Human. Humans. Male. Polymerase Chain Reaction. Transplantation Conditioning / methods. Transplantation, Homologous. Treatment Outcome. Viral Load


41. Liang X, Greffe B, Garrington T, Graham DK: Precursor natural killer cell leukemia. Pediatr Blood Cancer; 2008 Apr;50(4):876-8
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  • [Title] Precursor natural killer cell leukemia.
  • Natural killer (NK) cell tumors are a rare and heterogeneous group of disorders.
  • Immature NK cell tumors are less common, and are less recognized and defined than mature NK cell tumors.
  • There is insufficient experience of diagnosis and treatment with immature NK cell tumors, especially in pediatric patients.
  • Here we describe a pediatric patient with precursor NK cell leukemia and review the literature of the previously reported cases in children to further help characterize the diagnosis, treatment, and outcome.
  • [MeSH-major] Killer Cells, Natural / pathology. Leukemia / pathology. Stem Cells / pathology

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  • [Copyright] (c) 2008 Wiley-Liss, Inc.
  • (PMID = 17417789.001).
  • [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
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42. Gandhi J: Natural killer cell leukaemia. BMJ Case Rep; 2009;2009
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  • [Title] Natural killer cell leukaemia.
  • She was initially admitted with sepsis without an obvious cause but with a differential diagnosis of a haematological malignancy.
  • Her admission blood tests showed a mildly reduced white cell count and low platelets.
  • The patient underwent two bone marrow biopsies, a percutaneous liver biopsy and had flow cytometry of her ascitic fluid, which revealed the diagnosis of a natural killer cell leukaemia.

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  • [Cites] Leuk Lymphoma. 2004 Dec;45(12):2427-38 [15621755.001]
  • [Cites] Leukemia. 2005 Dec;19(12):2186-94 [16179910.001]
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  • (PMID = 21886653.001).
  • [ISSN] 1757-790X
  • [Journal-full-title] BMJ case reports
  • [ISO-abbreviation] BMJ Case Rep
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Other-IDs] NLM/ PMC3031875
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43. Zheng YY, Chen G, Zhou XG, Jin Y, Xie JL, Zhang SH, Zhang YN: [Retrospective analysis of 4 cases of the so-called blastic NK-cell lymphoma, with reference to the 2008 WHO classification of tumours of haematopoietic and lymphoid tissues]. Zhonghua Bing Li Xue Za Zhi; 2010 Sep;39(9):600-5
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] [Retrospective analysis of 4 cases of the so-called blastic NK-cell lymphoma, with reference to the 2008 WHO classification of tumours of haematopoietic and lymphoid tissues].
  • OBJECTIVE: To study the clinical and pathologic features of 4 cases of the so-called blastic natural killer (NK)-cell lymphoma, with reference to the 2008 WHO classification of tumours of haematopoietic and lymphoid tissues.
  • METHODS: The clinical, pathologic and immunohistochemical findings (EliVision method) of 4 cases of blastic NK-cell lymphoma (previously diagnosed according to the 2001 WHO classification) were retrospectively analyzed and reclassified with a special reference to the 2008 WHO classification.
  • RESULTS: The 4 cases of hematologic malignancy studied were characterized by the presence of medium-sized blastic lymphoma cells, CD56 expression, and absence of lineage-specific B-cell, T-cell and myeloid cell markers.
  • According to the 2001 WHO classification, they fell into the category of blastic NK-cell lymphoma.
  • They are likely derived from the plasmacytoid dendritic cells rather than NK cells.
  • They were then, according to the 2008 WHO classification, reclassified as the blastic plasmacytoid dendritic cell neoplasm.
  • This case was provisionally classified as a ambiguous lineage leukemia-NK cell lymphoblastic leukemia/lymphoma.
  • CONCLUSIONS: The so-called blastic NK-cell lymphomas in the 2001 WHO classification are rare and represent a heterogeneous group of lymphoproliferative disorders, with different clinical, pathologic and immunohistochemical features.
  • [MeSH-major] Precursor Cell Lymphoblastic Leukemia-Lymphoma / classification. Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology. Skin Neoplasms / classification. Skin Neoplasms / pathology
  • [MeSH-minor] Adult. Aged. Antigens, CD / metabolism. Antigens, CD56 / metabolism. Antigens, Differentiation, Myelomonocytic / metabolism. Humans. Interleukin-3 Receptor alpha Subunit / metabolism. Killer Cells, Natural / pathology. Middle Aged. Retrospective Studies. World Health Organization. Young Adult

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  • (PMID = 21092587.001).
  • [ISSN] 0529-5807
  • [Journal-full-title] Zhonghua bing li xue za zhi = Chinese journal of pathology
  • [ISO-abbreviation] Zhonghua Bing Li Xue Za Zhi
  • [Language] chi
  • [Publication-type] English Abstract; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] China
  • [Chemical-registry-number] 0 / Antigens, CD; 0 / Antigens, CD56; 0 / Antigens, Differentiation, Myelomonocytic; 0 / CD68 antigen, human; 0 / Interleukin-3 Receptor alpha Subunit
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44. 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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45. Ayyildiz O, Altintas A, Isikdogan A, Tuzcu A: Aggressive natural killer cell leukemia in a patient with common variable immunodeficiency syndrome. Gynecol Endocrinol; 2006 May;22(5):286-7
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  • [Title] Aggressive natural killer cell leukemia in a patient with common variable immunodeficiency syndrome.
  • [MeSH-major] Common Variable Immunodeficiency / complications. Killer Cells, Natural. Polyendocrinopathies, Autoimmune / complications. Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology

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  • [CommentOn] Gynecol Endocrinol. 2004 Jul;19(1):47-50 [15625773.001]
  • (PMID = 16785152.001).
  • [ISSN] 0951-3590
  • [Journal-full-title] Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology
  • [ISO-abbreviation] Gynecol. Endocrinol.
  • [Language] eng
  • [Publication-type] Case Reports; Comment; Letter
  • [Publication-country] England
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46. Suzuki S, Uozumi K, Utsunomiya A, Ishitsuka K, Masamoto I, Owatari S, Makino T, White Y, Arima N: Aggressive NK cell leukaemia after splenectomy: association with CD95-resistant memory T-cell proliferation and recalcitrant clinical course of haemophagocytic syndrome. Eur J Haematol; 2008 Sep;81(3):236-41
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  • [Title] Aggressive NK cell leukaemia after splenectomy: association with CD95-resistant memory T-cell proliferation and recalcitrant clinical course of haemophagocytic syndrome.
  • We describe a 44-yr-old Japanese woman with persistent polyclonal T-cell proliferation and recalcitrant clinical course of haemophagocytic syndrome (HPS).
  • T cells bearing alphabeta T-cell receptors (TCR) expressed increased amounts of CD95 and of CD45RO, which are phenotypically memory T cells.
  • Aggressive natural killer cell leukaemia (ANKL) without an association with Epstein-Barr virus was detected 1 month after therapeutic splenectomy that followed 3 yr of immunosuppressive therapy against HPS.
  • The immunophenotype of these leukaemia cells was CD56, CD16(dim), CD7, CD45RA and they expressed some CD2, CD8 and HLA-DR.
  • Latent NK-cell malignancy seemed to cause the CD95-resistant memory T-cell proliferation and splenectomy resulted in overt ANKL progression.
  • There should be careful consideration of the risks versus benefits of splenectomy in HPS, in light of the possibility of fatal leukaemia/lymphoma progression.
  • [MeSH-major] Antigens, CD95 / physiology. Killer Cells, Natural / immunology. Leukemia / immunology. Leukemia / therapy. Lymphohistiocytosis, Hemophagocytic / immunology. Lymphohistiocytosis, Hemophagocytic / therapy. Splenectomy / adverse effects
  • [MeSH-minor] Adult. Cell Proliferation. Chromosome Aberrations. Disease Progression. Fatal Outcome. Female. Flow Cytometry. Follow-Up Studies. Humans. Immunophenotyping. Immunosuppressive Agents / therapeutic use. Karyotyping. Risk Factors

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  • (PMID = 18510705.001).
  • [ISSN] 1600-0609
  • [Journal-full-title] European journal of haematology
  • [ISO-abbreviation] Eur. J. Haematol.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Denmark
  • [Chemical-registry-number] 0 / Antigens, CD95; 0 / Immunosuppressive Agents
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47. 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.
  • At level 1, six patients with extranodal NK/T-cell lymphoma, nasal type, were enrolled.
  • [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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48. 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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49. 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.
  • 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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  • [ISSN] 1687-9112
  • [Journal-full-title] Advances in hematology
  • [ISO-abbreviation] Adv Hematol
  • [Language] eng
  • [Publication-type] Journal Article
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50. 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

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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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51. Gubbels JA, Felder M, Horibata S, Belisle JA, Kapur A, Holden H, Petrie S, Migneault M, Rancourt C, Connor JP, Patankar MS: MUC16 provides immune protection by inhibiting synapse formation between NK and ovarian tumor cells. Mol Cancer; 2010 Jan 20;9:11
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  • [Title] MUC16 provides immune protection by inhibiting synapse formation between NK and ovarian tumor cells.
  • Here, we show that MUC16, a heavily glycosylated 3-5 million Da mucin expressed on the surface of ovarian tumor cells, inhibits the formation of immune synapses between NK cells and ovarian tumor targets.
  • RESULTS: Expression of low levels of MUC16 strongly correlated with an increased number of conjugates and activating immune synapses between ovarian tumor cells and primary naïve NK cells.
  • MUC16-knockdown ovarian tumor cells were more susceptible to lysis by primary NK cells than MUC16 expressing controls.
  • The NK cell leukemia cell line (NKL), which does not express KIRs but are positive for DNAM-1 and NKG2D, also conjugated and lysed MUC16-knockdown cells more efficiently than MUC16 expressing controls.
  • CONCLUSION: MUC16, a carrier of the tumor marker CA125, has previously been shown to facilitate ovarian tumor metastasis and inhibits NK cell mediated lysis of tumor targets.
  • Our data now demonstrates that MUC16 expressing ovarian cancer cells are protected from recognition by NK cells.

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  • (PMID = 20089172.001).
  • [ISSN] 1476-4598
  • [Journal-full-title] Molecular cancer
  • [ISO-abbreviation] Mol. Cancer
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / CA14520
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antigens, Differentiation, T-Lymphocyte; 0 / CA-125 Antigen; 0 / CD226 antigen; 0 / Histocompatibility Antigens Class I; 0 / KLRK1 protein, human; 0 / Ligands; 0 / MUC16 protein, human; 0 / Membrane Proteins; 0 / NK Cell Lectin-Like Receptor Subfamily K
  • [Other-IDs] NLM/ PMC2818693
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52. Skorupa A, Chaudhary UB, Lazarchick J: Cold agglutinin induced autoimmune hemolytic anemia and NK-cell leukemia: a new association. Am J Hematol; 2007 Jul;82(7):668-71
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  • [Title] Cold agglutinin induced autoimmune hemolytic anemia and NK-cell leukemia: a new association.
  • Cold agglutinin induced autoimmune hemolytic anemia is uncommonly associated with leukemia and lymphomas.
  • We present a case of a young Mexican female presenting with a cold agglutinin hemolytic anemia with expression of a rare Pr antigen specificity and an aggressive NK-cell leukemia.
  • [MeSH-major] Anemia, Hemolytic, Autoimmune / metabolism. Anemia, Hemolytic, Autoimmune / pathology. Killer Cells, Natural / metabolism. Killer Cells, Natural / pathology. Leukemia / metabolism. Leukemia / pathology


53. Guerrero A M, Lira V P, Bertin C P, Galleguillos V M, Ocqueteau T M: [Natural killer cell leukemia. Case report]. Rev Med Chil; 2005 Apr;133(4):457-60
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  • [Title] [Natural killer cell leukemia. Case report].
  • [Transliterated title] Leucemia de células natural killer. Caso clínico.
  • Natural killer leukemia is a rare and highly aggressive neoplasm, is more common in young male patients and has a very poor prognosis, with a median survival of few weeks.
  • Bone marrow aspiration and trephine biopsy showed an acute lymphoblastic leukemia.
  • The immunophenotype and immunohistochemistry revealed a natural killer acute leukemia.
  • The disease progressed rapidly and the patient died shortly after the diagnosis.
  • [MeSH-major] Killer Cells, Natural. Leukemia / pathology

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  • (PMID = 15953954.001).
  • [ISSN] 0034-9887
  • [Journal-full-title] Revista médica de Chile
  • [ISO-abbreviation] Rev Med Chil
  • [Language] spa
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] Chile
  • [Chemical-registry-number] 0 / Antigens, CD
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54. Grüllich C, Friske V, Finke J: Ex vivo detection of primary leukemia cells resistant to granule cytotoxin-induced cell death: a rapid isolation method to study granzyme-B-mediated cell death. Ann Hematol; 2008 Sep;87(9):701-8
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  • [Title] Ex vivo detection of primary leukemia cells resistant to granule cytotoxin-induced cell death: a rapid isolation method to study granzyme-B-mediated cell death.
  • Cytotoxic T lymphocytes and natural killer cells (CTL/NK) induce cell death in leukemia cells by the granzyme B (grB)-dependent granule cytotoxin (GC) pathway.
  • Resistance to GC may be involved in immune evasion of leukemia cells.
  • We developed a rapid method for the isolation of GC to investigate GC-mediated cell death in primary leukemia cells.
  • We isolated GC containing grB, grB complexes and PFN by detergent free hypotonic lysis of the human NK cell leukemia line YT.
  • The human leukemia cell lines KG-1, U937, K562 (myeloid leukemia), Jurkat, Daudi, and BV173 (lymphoblastic leukemia) treated with GC internalized grB and underwent cell death.
  • In primary leukemia cells analyzed ex vivo, we found GC-resistant leukemia cells in three out of seven patients with acute myeloid leukemia and one out of six patients with acute lymphoblastic leukemia.
  • We conclude that our method is fast (approximately 1 h) and yields active GC that induce grB-dependent cell death.
  • Furthermore, resistance to GC can be observed in acute leukemias and may be an important mechanism contributing to leukemia cell immune evasion.
  • [MeSH-major] Cell Death / drug effects. Cytotoxins / toxicity. Granzymes / toxicity. Leukemia / pathology
  • [MeSH-minor] Cell Line, Tumor. Drug Resistance, Neoplasm. Humans. K562 Cells / drug effects. K562 Cells / pathology. Killer Cells, Natural / immunology. Leukemia, Lymphocytic, Chronic, B-Cell / pathology. Leukemia, Myeloid, Acute / pathology. Perforin / metabolism. Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology. T-Lymphocytes, Cytotoxic / immunology. U937 Cells / drug effects. U937 Cells / pathology

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  • (PMID = 18437383.001).
  • [ISSN] 0939-5555
  • [Journal-full-title] Annals of hematology
  • [ISO-abbreviation] Ann. Hematol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Cytotoxins; 126465-35-8 / Perforin; EC 3.4.21.- / Granzymes
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