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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a case of an Epstein-Barr virus (EBV)-associated nasal-type natural killer cell lymphoma (NKCL) preceded by benign panniculitis, which arose in a 48-year-old woman with an asymptomatic human T-cell leukemia/lymphoma virus type-1 (HTLV-1) infection. A biopsy of the initial panniculitis lesion demonstrated lobular panniculitis with a germinal center composed of benign mononuclear cells with a phenotype of CD4+CD45RO+CD5sCD3+ cCD3 epsilon + T-cell intracellular antigen-1 (TIA-1)- and granzyme B-. One year after oral prednisolone therapy, the patient developed subcutaneous nodules composed of atypical lymphoid cells with a phenotype of CD4-CD45RO+CD56+sCD3-cCD3 epsilon + (TIA-1)+ and granzyme B+. In the initial panniculitis lesion, neither EBV-encoded RNA (EBER-1) nor clonal proliferation of EBV-infected cells was identified. In later lesions, however, a large number of atypical cells were positive for EBER-1, and a clonal expansion of EBV-infected cells was detected. No clonal rearrangement of T-cell receptor-alpha, -beta, or -gamma genes was found in either specimen. This patient was an asymptomatic carrier of human T-cell leukemia/lymphoma virus type-1 (HTLV-1) without clonal integration of proviral HTLV-1 in neither the peripheral blood nor the skin lesions. These observations suggest that EBV-associated NKCL occurred subsequently in the clinical course of benign panniculitis under the influence of immunosuppression caused by prednisolone treatment and HTLV-1 infection.
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PMID:Nasal-type natural killer cell lymphoma preceded by benign panniculitis arising in an asymptomatic HTLV-1 carrier. 1295 85

B-cell chronic lymphocytic leukemia (B-CLL) is the most common leukemia in the Western world. It is currently an incurable disease, making new treatment options such as immunotherapy desirable. Monoclonal antibodies (Mabs) to surface antigens of the tumor cell is one option. Administration of cytotoxic cells such as natural killer (NK) and natural killer-like T (NKT) cells expanded in vitro might be a useful treatment modality alone or in combination with MAbs. A limiting step in the development of successful cellular immunotherapy has been the availability of appropriate cytotoxic cells. Here, we report the feasibility of expanding populations of the human killer cells, CD3-CD56+ NK and CD3+CD56+ NKT cells, from peripheral blood mononuclear cells (PBMCs) of B-CLL patients. The influence of tumor B cells on the in vitro expansion of killer cells was assessed by depleting B cells from PBMCs by microbead separation before culture. The 21-day cultures from both B-cell- and non-B-cell-depleted PBMC showed a marked expansion of NK cells, and also of T cells, among which almost half had the NKT phenotype. Depletion of B cells before culture did not change the expansion rates of NK and NKT cells significantly. In patients with progressive B-CLL, NK cell expansion capacity was improved after fludarabine treatment when compared to samples obtained before treatment. Repeated samples of PBMCs from individual untreated patients with both indolent and progressive disease cultured under identical conditions gave similar NK cell expansion rates. Expanded killer cell populations had cytotoxic function against the NK-sensitive target K562 cell line and expressed high levels of Granzyme B. From our studies, we conclude that NK cells as well as NKT cells from the peripheral blood of B-CLL patients can be expanded, and that these cells have cytotoxic capacity.
Leukemia 2003 Oct
PMID:Expansion of natural killer (NK) and natural killer-like T (NKT)-cell populations derived from patients with B-chronic lymphocytic leukemia (B-CLL): a potential source for cellular immunotherapy. 1451 43

Clinical outcome in diffuse large B-cell lymphoma (DLBCL) remains unpredictable, despite the identification of clinical prognostic parameters. Here, we investigated in pretreatment biopsies of 70 patients with DLBCL whether numbers of activated cytotoxic T-lymphocytes (CTLs), as determined by the percentage of CD3-positive lymphocytes with granzyme B (GrB) expression, have similar prognostic value as found earlier in Hodgkin's lymphoma and anaplastic large-cell lymphoma and whether loss of major histocompatibility complex (MHC)-I molecules or expression of the GrB antagonist protease inhibitor 9 (PI9) may explain immune escape from CTL-mediated cell death. Independent of the International Prognostic Index (IPI), the presence of >/=15% activated CTLs was strongly associated with failure to reach complete remission, with a poor progression-free and overall survival time. Downregulation of MHC-I light- and/or heavy-chain expression was found in 41% of interpretable cases and in 19 of 56 interpretable cases PI9 expression was detected. We conclude that a high percentage of activated CTLs is a strong, IPI independent, indicator for an unfavorable clinical outcome in patients with primary nodal DLBCL. Although in part of DLBCL expression of PI9 and loss of MHC-I expression was found, providing a possible immune-escape mechanism in these cases, no correlation with clinical outcome was found.
Leukemia 2004 Mar
PMID:Prognostic significance of activated cytotoxic T-lymphocytes in primary nodal diffuse large B-cell lymphomas. 1471 86

In order to monitor the immunological status of patients after allogeneic hematopoietic stem cell transplantation(HSCT), granzyme B(GrB), perforin(PRF) and Fas ligand(L) antigens and mRNAs were measured by flow cytometry and real time RT-PCR, respectively. Cytoplasmic antigens were detected in whole blood after fixation and pretreatment with saponin. Real time PCR was carried out using extracted RNA from buffy coat. We measured these substances in a cytotoxic T cell clone, a natural killer cell line, and peripheral blood collected from 11 patients after HSCT. Although changes in antigen levels were not detected, increased levels of GrB and Fas L mRNAs were quantitatively measured in CTLs and NK cells stimulated by IL-2 combined with IL-12. Increased levels of GrB and/or PRF antigens were detected in four of five patients with chronic GVHD. Increased mRNA levels were also observed in one or more of GrB, PRF or Fas L in four of five patients with cGVHD, although there was a discrepancy between antigen and mRNA positivity. Four of six patients without cGVHD were positive for apoptosis-inducing factors, either by antigen detection or RT-PCR. One of these four had relapsing leukemia, and another had herpes zoster infection, while the reasons for positive results in the other two patients are not clear. Although changes in antigen levels did not parallel those in mRNA, measurement of these parameters may assist in predicting GVHD, GVL and infections following HSCT.
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PMID:[Levels of granzyme B, perforin and Fas ligand antigens and mRNAs in patients following allogeneic hematopoietic stem cell transplantation]. 1474 38

Chronic lymphocytic leukemia (CLL) is associated with increased risk of malignancy, but the occurrence of other lymphomas, in particular T-cell lymphomas, is rare. We identified 7 cases of peripheral T-cell malignancy associated with B-cell-derived CLL from the files of two institutions over a 20-year period. The presence of both B and T lymphoproliferative disorders was confirmed in all cases by immunophenotype and in 6 cases by gene rearrangements. Six patients developed peripheral T-cell lymphoma (PTCL), unspecified, during the course of CLL (10-168 months). In all 5 evaluable cases, the cells had a cytotoxic T-cell phenotype; the sixth case was CD56+, but TIA-1 and Granzyme B could not be studied. A seventh patient with CLL developed mycosis fungoides, and an aggressive NK cell leukemia. To investigate possible risk factors for the development of PTCL, we screened 100 unselected peripheral blood samples from newly diagnosed CLL patients by PCR for the presence of clonal T cell populations. We found evidence of clonal T-cell expansion in 8 patients and increased lymphocytes with large granular lymphocyte morphology in 7 of 8 cases. The immunophenotype was assessed by multicolor flow cytometry and in 4 cases the T-cell expansion was composed of either CD3+/CD8+ or CD3+/CD4-/CD8- cells. The cytotoxic nature of the clonal T-cell expansions in the peripheral blood correlates with the cytotoxic nature of the PTCLs, but their role in the subsequent development of T-cell lymphomas is still unclear. PTCL following CLL should be distinguished from typical Richter syndrome, which it can mimic clinically.
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PMID:Clonal T-cell populations and increased risk for cytotoxic T-cell lymphomas in B-CLL patients: clinicopathologic observations and molecular analysis. 1522 53

The oncoprotein Tax of human T-cell leukemia virus type I (HTLV-1) is the major mediator of viral pathogenesis in infected individuals. Expression of Tax under the regulation of the human granzyme B promoter in mice results in a lymphoproliferative disorder resembling adult T-cell leukemia/lymphoma (ATL). Tax expression is associated with the production of high levels interferon-gamma (IFN-gamma) in HTLV-1-infected CD4(+) cells and Tax-transgenic tumors. We examined the role of IFN-gamma in tumorigenesis, by mating Tax-transgenic mice with a gene-specific knockout for IFN-gamma. IFN-gamma(-/-) Tax(+)-transgenic mice show accelerated tumor onset (median, 4 versus 6 months), dissemination (median, 5 versus 7 months), and death (median, 7 versus 10 months), compared with IFN-gamma(+/-) or IFN-gamma(+/+) Tax(+) mice. Pathologic and immunophenotypic characteristics of tumors from all genotypes are indistinguishable, except for enhanced interleukin 2 receptor-beta (IL-2Rbeta) and suppressed intercellular adhesion molecule-1 (ICAM-1) expression on tumors from IFN-gamma(-/-) Tax(+) transgenic mice. IFN-gamma(-/-) tumors demonstrate enhanced CD31 (platelet-endothelial CAM-1 [PECAM-1]) staining compared with those from IFN-gamma(+/-) or IFN-gamma(+/+) Tax(+) mice. Angiogenesis-specific cDNA microarray analysis identified 4 mediators of angiogenic growth differentially expressed in tumors from Tax(+)IFN-gamma(-/-) mice compared with Tax(+)IFN-gamma(+/+) littermates. As confirmed by reverse transcription-polymerase chain reaction (RT-PCR), loss of IFN-gamma results in down-regulation of tumor necrosis factor-alpha (TNF-alpha) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) while up-regulating expression of vascular endothelial growth factor (VEGF) and tenascin C. These results provide insight into a possible mechanism by which IFN-gamma contributes to host resistance against HTLV-induced tumors through an angiostatic effect.
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PMID:Enhanced tumorigenesis in HTLV-1 tax-transgenic mice deficient in interferon-gamma. 1529 59

Anaplastic large-cell lymphoma (ALCL) is a distinct biological and cytogenetic entity with a broad spectrum of morphological features (common type, small-cell variant and lymphohistiocytic variant). Few cell lines of ALCL are available and they all originate from primary tumors demonstrating the common type morphology (ie large-sized lymphoma cells). We established a new ALCL cell line (COST) from the peripheral blood of a patient with a small-cell variant of ALCL, at diagnosis. Cells growing in vitro and in SCID mice consisted of two populations, that is, small- and large-sized cells as seen in the patient's tumor. Both large and small malignant cells were positive for CD43/MT1 T-cell associated antigen, perforin, granzyme B and TIA-1, but negative for CD2, CD3, CD5, CD7, CD4 and CD8 antigens. Standard cytogenetic studies as well as multiplex FISH confirmed the presence of the canonical t(2;5)(p23;q35) translocation, but also revealed additional numerical and structural abnormalities. The COST cell line is the first ALCL small-cell variant cell line, and thus provides a potentially useful tool for further functional and molecular studies that should improve our understanding of the small-cell variant of ALCL, which is more frequently complicated by a leukemic phase.
Leukemia 2004 Oct
PMID:Establishment of a novel anaplastic large-cell lymphoma-cell line (COST) from a 'small-cell variant' of ALCL. 1535 58

Cytotoxic T-cells (CTL) play a central role in the recovery of mammalian hosts from retroviral infections. However, the molecular pathways that mediate the antiretroviral activity of CTL are still elusive. Here we explore the protective role of the two main cytolytic pathways of CTL, that is, granule exocytosis and Fas/Fas ligand (FasL), in acute and persistent Friend retrovirus (FV) infection of mice. For this purpose, we have used mutant mouse strains with targeted gene defects in one or more components of the two cytolytic pathways including perforin, granzyme A, granzyme B, Fas, and FasL. The important function of CTL in resistance of C57BL/6 (B6) mice to FV is emphasized by the finding that depletion of CD8+ T-cells prior to virus infection resulted in severe splenomegaly and high viral loads in blood and spleen tissue. Analysis of primary FV infection in knockout mice revealed that acute infection was readily controlled in the absence of functional Fas. Most notably in the presence of Fas/FasL each of the three effector molecules of the exocytosis pathway (i.e., perforin, granzyme A, and granzyme B) was capable on its own to mediate suppression of virus replication and protection from leukemia. However, triple knockout mice lacking perforin and the two granzymes were fully susceptible to FV-induced leukemia. In contrast to acute infection the Fas/FasL pathway was mandatory for effective control of FV replication during persistent infection. These findings suggest novel pathways of CTL-mediated viral defense and contribute towards a better understanding of the molecular mechanisms of CTL activity in retroviral infections.
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PMID:Independent roles of perforin, granzymes, and Fas in the control of Friend retrovirus infection. 1556 31

A 78-year-old Japanese woman with adult T-cell leukaemia/lymphoma (ATL) presented with an unusual purpuric and erythematous eruption on the face and trunk. Immunohistochemical and flow cytometric analyses showed that the tumour cells were CD4/CD8 double-negative, and expressed CCR4 T-helper (Th) 2 chemokine receptors. Despite these features, the cells aberrantly produced granzyme B, which is a cytotoxic molecule usually produced by CD8(+) cytotoxic T cells, natural killer cells, or occasionally by Th1 cells. In a purpuric lesion, extravasation of erythrocytes was associated with an infiltrate of these cytotoxic tumour cells. Our case suggests phenotypical and functional heterogeneity of tumour cells in ATL, which may be closely related to the clinical appearance of the skin eruption.
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PMID:Purpuric adult T-cell leukaemia/lymphoma: expansion of unusual CD4/CD8 double-negative malignant T cells expressing CCR4 but bearing the cytotoxic molecule granzyme B. 1572 51

Microphthalmia transcription factor (MITF) and STAT3 are two transcription factors that play a major role in the regulation of growth and function of mast cells and melanocytes. We have previously provided experimental evidence regarding the functional cross-talk between MITF, protein inhibitor of activated STAT3, and STAT3 in response to cytokine activation of mast cells. Recent studies have demonstrated that binding of different IgE molecules to their FcepsilonRI induces a spectrum of intracellular events in the absence of specific Ag. In this work, we show for the first time that, in mouse bone marrow-derived mast cells and in rat basophilic leukemia cells, monomeric IgE alone can induce the MITF-protein inhibitor of activated STAT3-STAT3 network of interactions and leads to phosphorylation of MITF at S73 and of STAT3 at both tyrosine 705 and S727. This phosphorylation increases the transcriptional activity of MITF and STAT3 as indicated by mRNA accumulation of their target genes such as Bcl-2, granzyme B, and c-Myc. Interestingly, MITF and STAT3 were not found to be obligatory factors in the anti-apoptotic response induced by IgE. Thus, the phenomenon that IgE alone was able to induce transcription factors that are essential for mast cell function could contribute to our understanding of the pathogenesis of allergy and its associated diseases.
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PMID:Immunological trigger of mast cells by monomeric IgE: effect on microphthalmia transcription factor, STAT3 network of interactions. 1603 81


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