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1/16. Hodgkin and Reed-Sternberg-like cells in B-cell chronic lymphocytic leukemia represent the outgrowth of single germinal-center B-cell-derived clones: potential precursors of Hodgkin and reed-sternberg cells in Hodgkin's disease.

    In rare cases of B-cell chronic lymphocytic leukemia (B-CLL), large cells morphologically similar to or indistinguishable from Hodgkin/Reed-Sternberg (HRS) cells of Hodgkin's disease (HD) can be found in a background of otherwise typical B-CLL. To test these HRS-like cells for a potential clonal relationship to the B-CLL cells, single cells were micromanipulated from immunostained tissue sections, and rearranged immunoglobulin genes were amplified from HRS-like cells and B-CLL cells and sequenced. The same variable (V) gene rearrangements with shared and distinct somatic mutations were found in HRS-like and B-CLL cells from 1 patient, which indicates derivation of these cells from 2 distinct members of a germinal-center B-cell clone. Separate clonal V gene rearrangements were amplified from HRS-like and B-CLL cells from 2 other patients, showing concomitant presence of 2 distinct expanded B-cell clones. Epstein-Barr virus (EBV) was detected in the HRS-like cells of these 2 latter cases, indicating clonal expansion of an EBV-harboring B cell in the setting of B-CLL. There is evidence that HRS-like cells in B-CLL, like HRS cells in HD, derive from germinal-center B cells. In all cases, somatic mutations have been detected in the rearranged V genes of the HRS-like cells, and in 1 of the EBV-positive HRS-like cell clones, somatic mutations rendered an originally functional V gene rearrangement nonfunctional. We speculate that the HRS-like cells in B-CLL represent potential precursors for HRS cells causing HD.
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keywords = leukemia
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2/16. CD20-positive adult T-cell leukemia.

    A 67-year-old woman was admitted to our hospital because of lymphadenopathy and lymphocytosis. Monoclonal integration of HTLV-I provirus dna was detected, and a diagnosis of adult T-cell leukemia (ATL) was made. flow cytometry revealed that the ATL cells expressed CD20 as well as T-cell-associated antigens, and expression of CD20 mRNA was also demonstrated. A novel T-cell subpopulation expressing CD20 molecules has recently been identified. This is the first report of CD20-positive ATL, suggesting that HTLV-I can infect and transform CD20-positive T cells.
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keywords = leukemia
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3/16. acquired immunodeficiency syndrome-associated T-cell lymphoma: evidence for human immunodeficiency virus type 1-associated T-cell transformation.

    The majority of lymphomas in the setting of acquired, iatrogenic, or congenital immunodeficiencies are B-cell lymphoproliferations. We describe a rare T-cell lymphoma in a fulminantly ill patient infected with human immunodeficiency virus type 1 (hiv-1). The T-cell nature of the process was defined genotypically (monoclonal T-cell receptor beta-chain [CT beta] rearrangement) and phenotypically (CD45RO , CD4 , CD5 , CD25 , CD8-, CD3- and negative for a variety of B-cell and monocyte markers). The CD4 , CD25 (interleukin-2 receptor [IL-2R]) phenotype with production of IL-2 and IL-2R rna is analogous to human T-lymphotropic virus type I (HTLV-I)-associated adult T-cell leukemia/lymphoma (ATLL); however, no HTLV-1 could be detected. Southern blot analysis did demonstrate monoclonally integrated hiv-1 within the tumor genome. Furthermore, the tumor cells were producing HIV p24 antigen as shown by immunohistochemistry. This is the first case of acquired immunodeficiency syndrome (AIDS)-associated non-Hodgkin's lymphoma in which hiv-1 infection may have played a central role in the lymphocyte transformation process.
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keywords = leukemia
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4/16. Establishment and characterization of a bi-phenotypic leukemic cell line, NALM-19, from a patient with acute leukemia.

    Based on the immunophenotypic and genotypic findings, this acute leukemia cell line, designated NALM-19, is unique in that a partial expression of both B-cell and myeloid cell features are present in this single clonal leukemic cell population. It is noteworthy that two "normal" EB virus-transformed B cell lines, B239 and B240, (paired with NALM-19) were established from the same leukemic blood.
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5/16. Two t(9;22) leukemia cell lines (NALM-24 and NALM-25) with bi-phenotypic characteristics and an EBV-positive B-cell non-leukemia cell line (B262) established from a patient with acute lymphoblastic leukemia.

    Based on the immunophenotypic, cytogenetic and genotypic findings, two unique leukemia cell lines, NALM-24 and NALM-25, and an EBV-transformed "normal" B-lymphoblastoid cell line (B262) from a patient with ALL were established and characterized. NALM-24 and NALM-25 are unique in that expression of both show B cell and myeloid cell features with the t(9;22) chromosome in single clonal leukemic cell populations.
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keywords = leukemia
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6/16. Extra y chromosome in chronic lymphoproliferative disorders.

    Using separated lymphocytes from 95 male patients with B-cell lymphoproliferative disorders, we have established both Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines and short-term cultures with polyclonal B-cell mitogens. Cytogenetic studies of these patients revealed an extra y chromosome in 4 of 71 male cell lines examined. An extra y chromosome appeared to be the sole karyotype change (47,XY, Y) in 2 of these 4 patients. The extra y chromosome was accompanied by extra copies of chromosomes 12 and 21 (48,XY, Y, 12 and 48,XY, Y, 21) in the other 2 patients, respectively. The possible oncological role of the extra y chromosome in the initiation of leukemia is discussed.
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keywords = leukemia
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7/16. Spontaneous Epstein-Barr virus transformed B-cell line sharing the identical immunoglobulin gene rearrangement with acute myeloid leukemia.

    Mononuclear cells from a 44-year-old patient with acute myeloid leukemia (AML) gave rise to a spontaneous permanent cell line cultured in suspension. The cell line was shown to be positive for Epstein-Barr virus nuclear antigen (EBNA). As expected, its composite phenotype was of B-cell type with B-cell antigens (CD 20, CD 21) and with monoclonal surface IgM of kappa type, but without detectable IgM secretion. Surprisingly, identical monoclonal rearrangements of the immunoglobulin heavy chain (JH) sequences could be demonstrated in the uncultured bone marrow AML cells and in the cell line that also had kappa light chain gene rearrangement. This is the first case to our knowledge of an EBNA positive B-cell line with identical monoclonal Ig heavy chain rearrangement as detected in myeloblastic leukemia cells.
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ranking = 1.3205321157343
keywords = leukemia, myeloid leukemia
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8/16. Transformation of hairy cell leukemia to EBV genome-containing aggressive B cell lymphoma.

    Hairy cell leukemia is a preplasmacytic B cell leukemia which is not EBV associated, although elevated titers of Epstein-Barr virus (EBV) antibodies have been seen in this leukemia and chronic lymphocytic leukemia. Hairy cells are not readily susceptible to EBV infection in vitro, even though they are EBV receptor-positive B cells. We have observed a 59-year-old patient who after 9 years of hairy cell leukemia developed a well-differentiated IgG-kappa monoclonal B cell lymphoma without further evidence of hairy cell leukemia. Pathologically, the lymphoma showed plasmacytic differentiation, and in the patient's serum, a 2 g/dl monoclonal IgG-kappa component was present. dna extracted from the lymphomatous lymph node hybridized with dna fragments of a reiterated sequence of EBV, IR1. The transformation, with no chemotherapy involved, from a preplasmacytic leukemia into a lymphoplasmacytic lymphoma with monoclonal gammopathy may be related to the entry of EBV into these cells. Studies at the molecular level may help understand mechanisms of malignant transformation or interconversion in lymphoproliferative disorders of the B cell type.
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ranking = 2.2
keywords = leukemia
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9/16. Simultaneous presence of translocations t(14;18) and t(2;8) in a case of chronic lymphocytic leukemia.

    We report a patient with classical chronic lymphocytic leukemia of IgM kappa phenotype and a stable clinical course, in which repeated chromosome analyses of blood lymphocytes revealed the coexistence of t(14;18), a marker often associated with follicular low grade lymphocytic lymphomas, and t(2;8), a variant of the t(8;14) typically seen in Burkitt's lymphoma. Both these translocations involve immunoglobulin gene regions, the t(2;8) being almost always found in patients with kappa light chain restriction. However, in an EBV-immortalized cell line of this patient, most karyotypes contained t(14;18) alone, without the t(2;8). This suggests that t(14;18) was the primary cytogenetic event, and that t(2;8) evolved subsequently. As a secondary cytogenetic event, the t(2;8) may not share the grave clinical consequences of a primary t(2;8) as seen in Burkitt's lymphoma and related disorders.
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10/16. Regulation of human T-cell proliferation: T-cell growth factor and isolation of a new class of type-C retroviruses from human T-cells.

    The discovery, characterization, and purification of human T-cell growth factor (TCGF) has led to the establishment of continuously growing T-lymphoblast cell lines from normal people and from patients with certain T-cell neoplasias. In contrast to normal T-cells, neoplastic mature T-cells respond directly to TCGF, requiring no prior lectin or antigen in vitro activation. The transformed T-cell lines have phenotypic characteristics consistent with the neoplastic cells of their disease of origin. A novel retrovirus, human T-cell lymphoma-leukemia virus (HTLV), has been isolated from the fresh and cultured cells of two of these patients. Subsequent characterization of this virus has shown that it is not significantly related to any known animal retrovirus, is not an endogenous (genetically transmitted) virus of man, and so far has been associated only with fresh or cultured T-cells from patients with T-cell neoplasia. These results suggest that HTLV infected some mature T-cells of some people and that it might be involved in some neoplasias involving these cells.
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ranking = 0.2
keywords = leukemia
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