Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bcl-6 (LAZ-3) and Bcl-2 gene rearrangements have been respectively reported in 20-35 per cent and 10-25 per cent of diffuse large B-cell lymphomas (DLBCLs). Although these genetic lesions have been associated with different clinical outcomes (i.e., more favourable in Bcl-6 rearranged cases and poorer in Bcl-2 rearranged cases), their prognostic significance is still controversial. In the present study, we have investigated by Southern blot analysis the Bcl-6 and Bcl-2 gene configuration in a series of 80 lymph nodes involved by well-characterized DLBCLs, histologically defined according to the REAL and the updated Kiel classifications. The molecular findings have been correlated with the clinical features at presentation and with response to therapy. The majority of cases (57/80 = 71.2 per cent) had a centroblastic morphology. Bcl-6 rearrangements were detected in 23/80 cases (28.8 per cent), and were similarly associated with centroblastic (18/57 = 31.6 per cent) or immunoblastic (3/11 = 27.3 per cent) histotypes. In contrast, Bcl-2 was found to be rearranged in only three cases of centroblastic lymphoma (3.8 per cent). No significant differences were found between Bcl-6 rearranged and germline cases, as far as the clinical features at presentation are concerned. Forty-one patients, in whom the lymph node biopsy was performed at diagnosis, could be evaluated for response to treatment and clinical outcome. Most of these cases (30/41 = 73.2 per cent) were nodal DLBCL, without extranodal site involvement. Analysis of the clinical outcome showed no statistically significant differences between Bcl-6 rearranged and Bcl-6 germline cases (actuarial overall survival 50 per cent vs. 48 per cent, event-free survival 45 per cent vs. 46 per cent, at 4 years). These findings confirm that Bcl-6 rearrangements are the most frequent genetic lesion in DLBCL. The incidence of Bcl-2 involvement in our series is significantly lower than the figures reported in other studies, mainly from North American countries, probably reflecting heterogeneous patient selection and/or epidemiological variability. Finally, our results suggest that no relevant clinical differences are observed between Bcl-6 rearranged and Bcl-6 germline cases, when nodal DLBCLs are considered.
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PMID:Pathogenetic and clinical implications of Bcl-6 and Bcl-2 gene configuration in nodal diffuse large B-cell lymphomas. 942 82

The EBV plays a major role in the development of lymphoproliferative disorders in immunosuppressed patients. After organ transplantation most of lymphoproliferative disorders associated with EBV are polymorphic, with various expression of clonality. The pattern of EBV latency genes expression is rather the same as in lymphoblastoid cells lines and the EBV infected cells strongly expressed activation and adhesion molecules in most cases. In AIDS-related lymphomas the frequency of EBV as well as the expression of latency genes are related to the localization and to the histological subtypes. While EBV is observed in 30 to 50% of cases of Burkitt's lymphomas occurring the early stage of AIDS, its association in primary brain lymphomas and immunoblastic lymphomas developed in the late stage is observed in nearly all cases as well as in Hodgkin's disease. In primary brain lymphomas, the high expression of LMP-1 protein is correlated to the expression of BCL2 oncoprotein suggesting a transactivation of bcl2 by LMP-1 as it was reported in vitro. In non overt immunosuppressed patients the role of EBV is less clearly established, particularly in Burkitt's lymphoma where EBV is now considered as a cofactor. In B-cell lymphoma EBV is detected in about 5% of cases except in peculiar situations such as in lymphoma occurring in pleural cavity after longstanding pleural chronic inflammation and in Richter's syndrome with Reed-Sternberg-like cells. In peripheral T-cell lymphomas, EBV is observed in about 25% of cases, but its frequency varies with the histology and the localisation. EBV is present in nearly all cases of angio-immunoblastic type and in the nasal lymphoid proliferations developed from the NK cells. Detected in 30 to 80% in the Reed-Sternberg cells of Hodgkin's disease cases, the pathogenic significance of EBV remains to be determined in this disease.
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PMID:[Role of Epstein-Barr Virus in lymphoproliferative disorders]. 945 45

We investigated the relationship between drug resistance and Bcl-2/Bax in B-cell chronic lymphocytic leukaemia (B-CLL). Apoptosis was induced in vitro with chlorambucil and cell death was monitored by dual-labelled FACS analysis using Annexin V and propidium iodide. Bcl-2 and Bax protein expression was quantified using FACS and a correlation between drug-induced apoptosis and Bcl-2/Bax was established. Cells were then sorted into viable and nonviable populations according to their forward and side-scatter characteristics and re-analysed for Bcl-2/Bax. The most resistant cells had elevated Bcl-2 levels and low Bax expression. Furthermore, those cells which were undergoing apoptosis showed only a marginal reduction in Bcl-2 expression, but significantly elevated Bax expression following exposure to chlorambucil. The Bcl-2/Bax was significantly greater in the cell fractions resistant to chlorambucil-induced apoptosis. This observation further supports the suggestion that Bax is the pivotal protein in determining the fate of cells following apoptotic signals.
Leuk Lymphoma 1998 Jan
PMID:Elevated Bcl-2/Bax are a consistent feature of apoptosis resistance in B-cell chronic lymphocytic leukaemia and are correlated with in vivo chemoresistance. 951 6

The chromosomal translocation t(14;18) in lymphoma leads to an overproduction of the Bcl-2 protein on the basis of increased Bcl-2 mRNA levels. Whereas the juxtaposition of Bcl-2 with the Ig heavy chain locus causes a transcriptional activation, 70% of the lymphomas also produce Bcl-2-Ig fusion RNAs with Ig 3' ends. Using S1 nuclease protection assays that can discriminate between nuclear RNA precursors and spliced mRNA, we found that the fusion RNAs in t(14;18) cell lines exhibit an additional posttranscriptional processing advantage. Transfection experiments with artificial genes containing various Bcl-2 or Ig 3' ends show that this effect is (1) related to RNA splicing and/or nucleocytoplasmic transport; (2) independent of transcriptional activation by the heavy chain enhancer; (3) dependent on the presence of the JH-CH and C-gamma1 Ig introns; and (4) tissue specific for B cells. This constitutes a novel mechanism of oncogene deregulation unrelated to transcriptional activation or half-life prolongation. The data further support the existence of a tissue-specific posttranscriptional pathway of Ig regulation in B cells.
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PMID:The Ig heavy chain 3' end confers a posttranscriptional processing advantage to Bcl-2-IgH fusion RNA in t(14;18) lymphoma. 957 34

The bcl-2 proto-oncogene encodes an inner mitochondrial membrane protein that blocks apoptosis and programmed cell death in human lymphoid tissue. In this study a monospecific anti-human bcl-2 antibody that is reactive in formalin-fixed tissues was used with an avidin-biotin complex immunoperoxidase method to evaluate 41 cases of lymphoproliferative disorders of the salivary gland. The study cases were 26 primary salivary gland lymphomas (including 21 B-cell lymphomas four T-cell lymphomas and one true histiocytic lymphoma) and 15 cases of myoepithelial sialadenitis. Bcl-2 expression is restricted to the mantle zone and interfollicular lymphocytes around reactive germinal centers of myoepithelial sialadenitis. Seventeen of the 21 B-cell lymphomas were positive for bcl-2, and were composed of mucosa-associated lymphoid tissue (MALT), centrocytic, centroblastic-centrocytic and centroblastic lymphomas. Noticeably, all 11 cases of MALT lymphoma were bcl-2 positive. In contrast, staining for bcl-2 was present in only one of four cases of T-cell lymphomas and was negative in one true histiocytic lymphoma. The expression of bcl-2 protein was also investigated in the ductal systems and epimyoepithelial islands of salivary glands from patients with malignant lymphoma and myoepithelial sialadenitis. While salivary ducts in eight of 15 cases of myoepithelial sialadenitis immunostained for bcl-2, epimyoepithelial islands showed bcl-2 expression in only five cases of myoepithelial sialadenitis. We found that ductal cells in the salivary gland from patients with primary non-Hodgkin's lymphomas expressed bcl-2 protein. It was of interest that epimyoepithelial islands in all cases of MALT lymphoma displayed bcl-2 expression whereas other subtypes of B-cell lymphoma, T-cell lymphoma and true histiocytic lymphoma were invariably negative. These results indicate that bcl-2 is expressed in a wide variety of non-Hodgkin's lymphomas, especially when all 11 cases of MALT lymphoma are bcl-2 positive. Epimyoepithelial islands in MALT lymphoma express this oncoprotein, and their ability to induce bcl-2 synthesis resulted in the prevention of apoptosis and prolonged cell survival. Furthermore, the expression of bcl-2 protein in the lymphoma cells may be responsible for the induction of bcl-2 expression in the adjacent epimyoepithelial islands through a lymphocyte chemical mediator.
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PMID:Detection of the apoptosis-suppressing oncoprotein bcl-2 in salivary gland lymphoma. 958 34

Bcl-2 (B cell leukemia/lymphoma-2), one of apoptosis-suppressing genes, can inhibit apoptosis of both some normal and tumor cells, and is related to the development of some tumors. In present study, the expression of bcl-2 was examined in 26 cases of oral lymphomas of mucosa associated lymphoid tissue (LMALT) using immunohistochemistry. The results showed that 73% of LMALT were positive to bcl-2 antibody. Among three main histological subtypes, the small-cleaved cell type demonstrated highest positive persentage (83%), followed by lymphoplasmacytoid lymphoma (71%) and lymphoplasmacytic lymphoma (51%). In respect to immunological subtypes, bcl-2 was detected in 69% of B cell lymphoma, 75% of T cell lymphoma, and 83% of lymphomas which could not be classified by present immunohistochemistry repectively. The results indicated that the inhibition of apoptosis might not be one of reasons for the development of some LMALT.
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PMID:[Expression of Bcl-2 gene product in oral lymphoma of mucosa associated lymphoid tissue]. 959 54

We studied overexpression of p53, Bcl-2, Bcl-6, c-Myc and Mdm2 proteins by immunohistochemistry for a total of 27 primary central nervous system B cell lymphomas (CNS lymphomas) in immunocompetent patients and one CNS lymphoma in an AIDS patient. The expression of Epstein-Barr (EB) virus-encoded small RNA-1 (EBER-1) was also analysed using in situ hybridisation. Overexpression (more than 20% of cells stained) of p53 protein was detected in 8 of 27 immunocompetent cases (30%); 6 cases showed a nuclear stain and 2 cases showed cytoplasmic stain (nuclear exclusion). Strong Bcl-2 or Bcl-6 immunoreactivity suggestive of overexpression was seen, respectively, in 5 (19%) and 6 (22%) cases; 2 cases were positive for both immunoreactivities. Interestingly, overexpression of Bcl-2 or Bcl-6 was not seen in the cases which showed p53 overexpression (P < 0.03; chi-square test). EBER-1 expression was not detected in any of the 27 immunocompetent cases, but was found in the AIDS-related CNS lymphoma, which also showed an overexpression of Bcl-6, but not Bcl-2. None of the cases showed c-Myc or Mdm2 overexpression. Taken together, it is suggested that CNS lymphoma in immunocompetent hosts is a distinct disease that has a different molecular profile from those of systemic lymphoma and/or AIDS-related CNS lymphoma.
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PMID:Expression of oncogenic molecules in primary central nervous system lymphomas in immunocompetent patients. 960 May 97

Bcl-2 overexpression has been shown to be associated with several malignancies, including B-cell chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphomas (NHL), mainly low-grade and follicular in type. It has as yet not been described in hairy cell leukemia (HCL). In 30 patients with CLL and 14 with HCL who were consecutively selected for treatment with purine analogues (Fludarabine in CLL and 2-chloro-deoxy-adenosine in HCL), we evaluated bcl-2 oncoprotein expression in leukemic cells on marrow sections that were taken before treatment and stained immunohistochemically with a monoclonal antibody (Dakopatts 124 clone), by the avidin-biotin-peroxidase method. All samples were found to be bcl-2 positive, with a staining intensity that was moderate to strong in CLL and weak to moderate in HCL. 83% of CLL and 100% of HCL patients were responsive to purine analogues. These findings show that bcl-2 is overexpressed in almost all cases CLL and HCL and that bcl-2 overexpression does not predict a poor response to purine analogues, which are believed to induce apoptosis.
Leuk Lymphoma 1998 Feb
PMID:BCL-2 immunohistochemical evaluation in B-cell chronic lymphocytic leukemia and hairy cell leukemia before treatment with fludarabine and 2-chloro-deoxy-adenosine. 961 87

The major vault lung resistance protein LRP is a cytoplasmic protein involved in drug resistance, especially in acute myeloid leukemia. We looked for LRP overexpression, using immunocytochemistry with LRP 56 monoclonal antibody, on marrow slides from 41 cases of myelodysplastic syndromes (MDS). LRP overexpression (LRP+) was defined by expression of LRP 56 in at least 20% of marrow blasts. LRP overexpression was seen in 19 (46%) cases. Concordant results between LRP overexpression and P-glycoprotein (PGP) expression were seen in 66% of the cases (p = 0.03), and discordant results (LRP+ and PGP-, or LRP- and PGP+) in 33% of the cases. No correlation was seen between LRP overexpression and FAB type, karyotype, CD34, p53 expression and bcl2 overexpression in blasts. Furthermore, in the 18 cases treated with anthracycline-AraC intensive chemotherapy and the 7 cases treated with low dose AraC, the response rate was not significantly different in LRP+ and LRP- patients. Survival was also similar in LRP+ and LRP- patients. In conclusion, LRP overexpression is probably more frequent in MDS than in de novo AML and, as in AML, is only partially correlated with PGP expression. In our experience, however, LRP was not a prognostic factor for response to chemotherapy and survival in MDS.
Leuk Lymphoma 1998 May
PMID:Expression of lung resistance protein and correlation with other drug resistance proteins and outcome in myelodysplastic syndromes. 964 68

The requirement for caspases (ICE-like proteases) were investigated in mediating apoptosis of WEHI7.2 mouse lymphoma cells in response to two death inducers with different mechanisms of action, the glucocorticoid hormone dexamethasone (DX) and the calcium-ATPase inhibitor thapsigargin (TG). Apoptosis induction by these agents followed different kinetics, and was closely correlated with in vivo activation of caspase-3 (CPP32/Yama/Apopain) and cleavage of the caspase target protein poly(ADP-ribose) polymerase (PARP). Caspase activation and PARP cleavage were inhibited by Bcl-2 overexpression. Cell extracts from DX- and TG-treated cells cleaved the in vitro synthesized baculovirus p35 ICE-like protease target, producing 25 and 10 kDa fragments. p35 cleavage was inhibited by mutating the active site aspartic acid to alanine, and by a panel of protease inhibitors that inhibit caspase-3-like proteases, including iodoacetamide, N-ethylmaleimide, and Ac-DEVD-cho. Treatment of cells in vivo with two cell permeant peptide fluoromethylketone inhibitors of caspase activity, Z-VAD-fmk and Z-DEVD-fmk, inhibited DX- and TG-induced apoptotic nuclear changes and maintained plasma membrane integrity, whereas the cathepsin inhibitor, Z-FA-fmk, and two calpain inhibitors failed to inhibit apoptosis. An unexpected observation was that due to the delayed time course of DX-induced apoptosis, optimal preservation of plasma membrane integrity was achieved by adding caspase inhibitors beginning 8 h after DX addition. In summary, the findings indicate that two diverse apoptosis-inducing signals converge into a common Bcl-2-regulated pathway that leads to caspase activation and apoptosis.
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PMID:Apoptosis induction by the glucocorticoid hormone dexamethasone and the calcium-ATPase inhibitor thapsigargin involves Bc1-2 regulated caspase activation. 970 90


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