Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:A9QXG9 (bcl-2)
 7,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A strictly stroma-dependent hematopoietic clone, Myl-D-7, with lympho-myeloid potential has been isolated. A subset of cells expresses myeloid-macrophage (Mac-1 and Gr-1), erythroid (TER119), and lymphoid (Thy-1 and B220) lineage markers. Spontaneous differentiation to the myeloid-macrophage, erythroid, or lymphoid pathway can be seen by morphologic criteria, detection of beta major globin synthesis, or expression of the early lymphoid specific transcription factor, Ikaros. By sorting lineage marker (Mac-1, Gr-1, B220, and TER119)-negative (LIN-) cells, we showed that the LIN- population actively self-renews on top of MS-5 stromal cells, and differentiates to LIN+ cells. Removal of stroma induces apoptosis and none of the growth factors tested can prevent apoptosis. Granulocyte-macrophage colony-stimulating factor accelerates the differentiation towards the myeloid-macrophage lineage. Using this clone, we show that (1) contact with stroma induces expression of bcl-2, (2) stromal cells derived from SI/SI homozygous fetuses can support long-term growth, and (3) conditioned media of specific stromal cells contains an activity that supports proliferation and self-renewal of the clone. Myl-D-7 can thus be used as an indicator cell for unknown factors that may provide stromal cell support.
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PMID:A novel hematopoietic multilineage clone, Myl-D-7, is stromal cell-dependent and supported by an alternative mechanism(s) independent of stem cell factor/c-kit interaction. 860 37

Mouse malignant T-lymphoma CS-21 cells can survive and proliferate in vitro when co-cultured with CA-12 stromal cells isolated from lymph nodes, but CS-21 cells undergo apoptotic cell death with DNA fragmentation when cultured alone. We immunized rats with CS-21 cells and raised monoclonal antibodies (MAbs) that recognized Thy-1 (CD90) or CD45 protein. The majority of these MAbs were able to inhibit the adhesion and apoptosis of CS-21 cells. When anti-Thy-1 MAbs were examined for their recognition site on Thy-1 glycoprotein, one of them, MCS-34, was found to recognize both Thy-1.1 and Thy-1.2. In addition, MCS-34, just like the anti-Thy-1 MAb G7, recognized the Thy-1A epitope. G7 was known to induce apoptosis in some T-cell hybridomas and in thymocytes. In CS-21 cells, however, G7 could not induce apoptosis, but MCS-34 could. Interestingly, MCS-34 enhanced the expression of bcl-2 protein, in spite of its ability to induce apoptosis. Upon examining the apoptosis-inducing mechanisms of MCS-34, we found that it promoted a sustained increase in cytoplasmic-free calcium in CS-21 cells. Calcium ionophore A23187 was also found to induce apoptosis in a dose-dependent manner. These results indicate that a sustained increase in cytoplasmic-free calcium by MCS-34 induces apoptosis in CS-21 cells in spite of bcl-2 protein expression.
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PMID:A novel anti-Thy-1 (CD90) monoclonal antibody induces apoptosis in mouse malignant T-lymphoma cells in spite of inducing bcl-2 expression. 863 72

We recently discovered the Kaposi's sarcoma-associated herpes virus (KSHV/HHV-8) in an uncommon and unusual subset of AIDS-related lymphomas that grow mainly in the body cavities as lymphomatous effusions without an identifiable contiguous tumor mass. The consistent presence of KSHV and certain other distinctive features of these body cavity-based lymphomas suggest that they represent a distinct entity. We tested this hypothesis by investigating 19 malignant lymphomatous effusions occurring in the absence of a contiguous tumor mass for their clinical, morphologic, immunophenotypic, viral, and molecular characteristics, KSHV was present in 15 of 19 lymphomas. All four KSHV-negative lymphomatous effusions exhibited Burkitt or Burkitt-like morphology and c-myc gene rearrangements and, therefore, appeared to be Burkitt-type lymphomas occurring in the body cavities. In contrast, all 15 KSHV-positive lymphomatous effusions exhibited a distinctive morphology bridging large-cell immunoblastic lymphoma and anaplastic large-cell lymphoma, and all 12 cases studied lacked c-myc gene rearrangements. In addition, these lymphomas occurred in men (15/15), frequently but not exclusively in association with HIV infection (13/15), in which homosexuality was a risk factor (13/13), presented initially as a lymphomatous effusion (14/15), remained localized to the body cavity of origin (13/15), expressed CD45 (15/15) and one or more activation-associated antigens (9/10) in the frequent absence of B-cell-associated antigens (11/15), exhibited clonal immunoglobulin gene rearrangements (13/13), contained Epstein-Barr virus (14/15), and lacked bcl-2, bcl-6, ras and p53 gene alterations (13/15). These findings strongly suggest that the KSHV-positive malignant lymphomatous effusions represent a distinct clinicopathologic and biologic entity and should be distinguished from other malignant lymphomas occurring in the body cavities. Therefore, we recommend that these malignant lymphomas be designated primary effusion lymphomas (PEL), rather than body cavity-based lymphomas, since this term describes them more accurately and avoids their confusion with other malignant lymphomas that occur in the body cavities. We further recommend that these PEL be considered for inclusion as a new entity in the Revised European-American Lymphoma Classification.
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PMID:Primary effusion lymphoma: a distinct clinicopathologic entity associated with the Kaposi's sarcoma-associated herpes virus. 869 12

Apoptosis plays a critical role during T cell development, both in the generation of functionally competent T cells in the thymus and the regulation of peripheral T cell populations. The fate of any T cell, whether it is developing in the thymus, or functioning in the peripheral immune system, is dependent on T cell receptor (TCR) specificity for antigens presented by MHC molecules and on the consequences of TCR-generated intracellular signalling pathways which lead to activation, anergy or apoptosis. This review describes data that have elucidated the way in which these highly regulated TCR-derived signalling pathways lead to such diverse final outcomes in thymocytes. Contributions to the induction of apoptosis in thymocytes by signalling pathways and receptors such as Fas, CD45 and CD28 are summarized, particularly with regard to the analysis of relevant transgenic mice. Developments concerning regulation of apoptosis by bcl-2 family members and the possible effectors of apoptosis, proteases, are assessed. Finally, this information is contrasted with the relatively scarce data on signalling pathways in thymic-derived T-ALL cells together with potential explanations of how transformation might occur by perturbation of apoptotic mechanisms. Precise understanding of these pathways may lead to the development of novel therapeutic reagents.
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PMID:The role of intracellular signalling pathways regulating thymocyte and leukemic T cell apoptosis. 875 58

Recent information is limited regarding pathological features of the malignant lymphomas of Africa, other than Burkitt's lymphoma. In this study, we apply modern techniques and nomenclature to classify 73 lymphomas from a central histopathology laboratory serving 40 mission hospitals in Kenya. We were particularly interested in the frequency of recently recognized lymphomas and the incidence of Epstein-Barr virus in various lymphoma subtypes. Malignant lymphomas accounted for 12% of all surgical pathology specimens processed in the laboratory over the 21-month period included in the study. Patient age ranged from 4 to 97 years (median, 35 years). The male-to-female ratio was 2.5:1. Sixty lymphomas (82%) were non-Hodgkin's, and 13 (18%) were Hodgkin's disease. Of the non-Hodgkin's lymphomas (NHLs), 52 (87%) were B-lineage, including 21 (35% of NHLs) Burkitt's lymphomas (only one from the jaw), 11 (18%) diffuse large B cell lymphomas; nine (15%) small lymphocytic lymphomas, six (10%) Burkitt's-like lymphomas, two (3%) follicular lymphomas (two of two expressed bcl-2 protein; one of two showed bcl-2 major breakpoint region rearrangement), two (3%) mantle cell lymphomas, and one extranodal marginal zone lymphoma. Of the eight T cell lymphomas, six were precursor T-cell type, and the remaining two were peripheral T cell lymphomas, unspecified. The median age of the 13 patients (18% of lymphomas) with Hodgkin's disease was 23 years (range, 9 to 97 years). Six were nodular sclerosis, four were mixed cellularity, one case each was lymphocyte depletion, lymphocyte predominance, and unclassified Hodgkin's disease. Hodgkin's cells in 6 of the 12 nonlymphocyte predominance cases were positive for CD20, and in three of the six for CD45 as well. Epstein-Barr virus was identified using in situ hybridization for EBER 1 in the malignant cells of 22 of 39 informative lymphomas, including each of 17 Burkitt's lymphomas, and three of seven diffuse large B cell lymphomas. Of note, none of five Burkitt's-like lymphomas expressed EBER 1. One of two informative cases of peripheral T cell lymphoma, and four of nine cases of Hodgkin's disease were EBER 1 positive. In summary, T cell lymphomas and recently recognized B-lineage non-Hodgkin's lymphoma subtypes do not appear to be particularly common in East Africa.
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PMID:The malignant lymphomas of Kenya: morphology, immunophenotype, and frequency of Epstein-Barr virus in 73 cases. 930 26

The malignant plasma cells from patients with multiple myeloma display considerable phenotypic heterogeneity. All plasma cells express high intensity CD38 (CD38++), cytoplasmic immunoglobulin and either kappa or lambda light chains. Subpopulations of mature (CD45-), immature (CD45+) and primitive (CD45++, CD19+) plasma cells can be defined but little is known about the functional differences and clinical significance of these subpopulations. Three colour flow cytometry and permeabilisation was used to determine the expression of functionally important antigens in plasma cell subpopulations. These antigens included the labelling index (LI, bromodeoxyuridine), number of nucleoside transporter per cell, p-glycoprotein (JSB-1), and oncoprotein expression (c-myc, c-fos, c-neu, bcl-2, p-ras, p53m, p-53w, and Rb). In progressive disease there was an increase in the absolute number but not the percentage of CD45++ plasma cells. There was a significant difference in the mean LI of the CD38++, CD45++ population in progressive disease compared with stable disease (9.2% vs 2.2%; z = 19.9, p < 0.001). The LI of CD45++ cells ranged up to 45% and provided a better correlation with disease status than the LI of the total cell population. Any increase in nucleoside transporters or p-glycoprotein expression was almost entirely attributable to an increase in the primitive plasma cell population. In 96% (n = 28) of samples from patients in progressive disease there was at least one abnormality in the functional phenotype of the primitive plasma cells. This is in contrast with 44% of samples from patients in stable disease (n = 58). These studies suggest that the functional phenotype of the primitive plasma cell determines the clinical phenotype of patients with myeloma.
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PMID:The functional phenotype of the primitive plasma cell in patients with multiple myeloma correlates with the clinical state. 937 99

Eight myeloma cell lines with variable expression of bcl-2 were screened for the expression of the FAS antigen and for sensitivity to anti-FAS-induced apoptosis. Anti-FAS-induced apoptosis correlated positively (R = 0.89) with the level of expression of the FAS antigen, and was independent of the expression of bcl-2. Forced expression of bcl-2 in 8226 and ARP-1 multiple myeloma (MM) cell lines expressing relatively low levels of bcl-2, resulted in 1-2 log increase in resistance to dexamethasone (DEX)-induced apoptosis. However, sensitivity to anti-FAS-induced apoptosis was unchanged in ARP-1 cells or was increased in 8226 cells, compared to the parental cell lines. The increased sensitivity to anti-FAS-induced apoptosis in 8226 cells was due to the increase in FAS expression in the bcl-2 transfected cells and was proportionate to the increase in FAS expression. Furthermore, we observed manyfold increase in the expression of Fas, CD40, CD45 and CD19 antigens, in 8226 cells, concomitant with a significant decrease in the expression of CD38 antigen. Thus, 8226 cells overexpressing bcl-2 appear to have an immature myeloma cell phenotype, have higher growth-rate and increased sensitivity to anti-FAS-induced apoptosis.
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PMID:Fas (APO-1/CD95)-mediated apoptosis is independent of bcl-2: a study with cell lines overexpressing bcl-2 and with bcl-2 transfected cell lines. 945 7

We report the case of a 53 year-old woman with a gastric tumor showing morphological, phenotypical and molecular features of a plasmablastic lymphoma, a recently recognized subtype of diffuse large B-cell lymphoma. The tumor was composed of plasmablast-like cells, lacked CD45 and B-cell associated antigens, expressed the plasma cell-associated antigen CD38, and showed clonally rearranged IgH genes in the absence of bcl-2 and bcl-6 genes rearrangement.
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PMID:Plasmablastic lymphoma of the stomach. A case report. 954 26

We report a series of 31 cases of splenic marginal zone lymphomas with an enlarged spleen and a multimicronodular macroscopic pattern. Two groups, A and B, were distinguished based on the presence (A) or absence (B) of a lymphoplasmacytic component with monoclonal immunoglobulin expression in the cytoplasm. There were no differences between the groups as far as age, sex, spleen weight, and progression. The only difference was the presence in group A of a monoclonal serum component and autoimmune disorders, particularly autoimmune hemolytic anemia. In most cases in which a liver and/or bone marrow biopsy was performed, lymphomatous infiltration was detected. Seven cases had a seric monoclonal IgM of 5 g/L or more and liver or bone marrow infiltration, corresponding to the definition of Waldenstrom's macroglobulinemia. Lymphoma cells had a monocytoid, centrocytoid and, in group A, lymphoplasmacytic morphology. The lymphomatous cells were positive for CD20, CD45 RA, and bcl-2. They expressed IgD in 9 cases, partially in 6, and were negative for IgD in 9 of the 24 cases studied. Progression seems to be slow, with a long survival. Three patients presented with transformation into a large B-cell lymphoma, which was responsible for death in two patients.
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PMID:Splenic marginal zone lymphoma with or without plasmacytic differentiation. 1111 78

Multiple myeloma (MM) is an incurable disease; therefore, there is a need for new modalities of treatment for this disease. We designed a study to test the sensitivity of MM cell lines, freshly isolated myeloma cells, and CD34(+) hematopoietic progenitor cells to adenovirus-mediated delivery of wild-type p53 (Ad-p53). Replication-deficient Ad-p53, previously used in phase I-II clinical trial for treatment of patients with solid tumors, was used in this study. Myeloma cells from seven MM cell lines with mutated or w.t. p53 and varying expression of bcl-2 were used. Fresh myeloma cells (CD38(bright)CD45(-)) and fresh CD34(+) hematopoietic stem cells and CD34(-) cells were purified by flow sorting of apheresis collections of MM patients undergoing high-dose chemotherapy and stem cell rescue. The effect of Ad-p53 on colony-forming unit granulocyte-macrophage (CFU-GM) and burst-forming unit erythroid (BFU-E) colony formation in methylcellulose was tested on purified CD34(+) and CD34(-) cells to evaluate bone marrow toxicity. Myeloma cells from cell lines, or freshly isolated myeloma cells, were sensitive to Ad-p53 only if they had mutated p53 and had low expression of bcl-2. CD34(+) cells were resistant to Ad-p53-mediated apoptosis, and CFU-GM and BFU-E colony formation was not affected by treatment with Ad-p53.Ad-p53 is a potent inducer of apoptosis in MM cell lines and in freshly isolated myeloma cells expressing low levels of bcl-2. Ad-p53 is not overtly cytotoxic to normal hematopoietic stem cells or normal lymphocytes; therefore, it could be considered for a phase I clinical trial of MM patients with mutated p53.
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PMID:Adenovirus-mediated delivery of p53 results in substantial apoptosis to myeloma cells and is not cytotoxic to flow-sorted CD34(+) hematopoietic progenitor cells and normal lymphocytes. 1114 57


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