UNIPROT:P10415 - FACTA Search

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Query: UNIPROT:P10415 (Bcl-2)
33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined c-Myc and Bcl-2 protein expressions during the induction of apoptosis and differentiation in TNF alpha-treated HL-60 cells using a two-color flow cytometric method. We found that c-Myc protein was rapidly down-regulated in the apoptotic cells while Bcl-2 protein was expressed at relatively high levels. Concomitantly with terminal differentiation Bcl-2 protein was down-regulated in differentiating cells as well as c-Myc protein. We also showed that c-myc antisense oligonucleotides could induce apoptosis in HL-60 cells whereas bcl-2 antisense did not induce apoptosis during the early time of treatment. These results suggest that the down-regulation of c-Myc protein expression is a primary event to induce apoptosis and neither consistent expression of c-Myc protein nor rapid down-regulation of Bcl-2 protein is necessary for the initial processing of apoptosis in HL-60 cells. Furthermore, concomitant down-regulation of c-Myc and Bcl-2 is closely associated with terminal differentiation and apoptotic cell death of HL-60 cells treated with TNF alpha.
Leuk Lymphoma 1996 Oct
PMID:C-Myc and Bcl-2 protein expression during the induction of apoptosis and differentiation in TNF alpha-treated HL-60 cells. 903 Nov 21

It has been thought that there is a particular balance between interferon and humoral immunity in the specific antiviral activity exerted by these systems. A possible relationship has been observed between some interferon-related proteins and the interferon serum level and a predictive significance can be assigned to MxA protein regarding the progression of some haematological malignancies. Both natural and recombinant interferon have been shown to be effective in the treatment of T-cell cutaneous lymphoma and the myeloma cell expression of Bcl-2 oncoprotein correlates to the response to interferon therapy in multiple myeloma patients. It has been thought that the combined therapy including interferon and cis-retinoic acid might be effective in the therapy of metastatic melanoma and breast cancer, whereas the combination of interferon with other chemotherapeutic agents appears to be effective in the treatment of hepatocellular cancer. It has been confirmed that interferon-alpha is useful in the therapy of chronic hepatitis C and a better knowledge regarding the mechanism of action of beta interferon in the therapy of multiple sclerosis has been acquired. Finally, a remarkable report regards the effectiveness of interferon in the therapy of idiopatic dilated cardiomiopathy.
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PMID:[Clinical use of interferon]. 911 15

The bcl-2 gene encodes a mitochondrial protein that inhibits the onset of apoptosis induced by growth factor withdrawal or cytotoxic agents. Using quantitative flow cytometry and expressing bcl-2 levels as the number of molecules of equivalent soluble fluorochrome (MESF) per cell, we have shown that bcl-2 protein expression in the blast cells from patients with acute myeloblastic leukaemia (AML) is heterogeneous, but not related to FAB type. The blast cells from AML patients with the capacity to grow and survive autonomously in vitro were found to have higher bcl-2 MESF values than those that were dependent upon exogenous growth factors. We have previously reported that the blast cells from 70% of AML patients exhibit autonomous growth and autocrine growth factor production in vitro and that this has been shown to be an important indicator of poor prognosis in AML. High bcl-2 expression has also been associated with a low complete remission rate and poor survival in AML. In the patients whose blast cells exhibited autonomous growth, neutralisation of endogenous GM-CSF resulted in down-regulation of bcl-2 protein, whereas in blast cells from patients whose cells proliferated only in the presence of added growth factors, incorporation of recombinant human (rh) GM-CSF in the culture media resulted in up-regulation of bcl-2. Because CD34 positivity has been reported as another indicator of poor prognosis in AML, we compared bcl-2 expression in cases of CD34 positive AML, CD34 negative AML and CD34 positive normal bone marrow cells. Bcl-2 was found to be strongly expressed on the CD34+ normal bone marrow cells. The blast cells from CD34+ AML patients expressed significantly higher bcl-2 levels than CD34- AML patients. In five cases of CD34+ AML, the bcl-2 levels were determined on purified CD34+ and CD34- blast cell populations. The CD34+ blast cells were found to express significantly higher bcl-2 levels compared with the CD34-blast cells. Our data would suggest that quantification of bcl-2 in AML blast cell may be useful as a prognostic indicator in AML.
Leuk Lymphoma 1997 Jan
PMID:Bcl-2 expression in acute myeloblastic leukaemia: relationship with autonomous growth and CD34 antigen expression. 915 52

Bcl-2 suppresses drug-induced apoptosis in vitro, although in many cases, this results only in a delayed onset of cell death. In vivo survival signals from the extracellular environment may also contribute to drug resistance and may act with Bcl-2 to promote long-term cell survival. Ligation of CD40 on B-lymphocytes in germinal centers (GCs) can suppress apoptosis induced by calcium ionophore or anti-IgM in vitro. We asked whether a combination of Bcl-2 expression and the provision of a culture environment that mimicked that of the GC [CD40 ligation and interleukin 4 (IL-4)] could increase the ability of B lymphoma cells to resist drug-induced apoptosis. A Burkitt lymphoma (BL) cell line transfected with either human bcl-2 (BL-bcl-2) or control plasmid (BL-Sv2) was used to examine the effects of Bcl-2 overexpression on the cellular response and long-term survival after treatment with the DNA-alkylating drug chlorambucil (CMB) in the presence or absence of CD40 ligation and IL-4. Administration of 20 microM CMB completely prevented cell proliferation. This was associated with an increase in p53 protein levels within 24 h, without an elevation in p21, Bax, or Mdm2 proteins. Analyses of cell cycle distribution and of cyclin B expression demonstrated that both cell lines arrested at G2/M, where they died. Fifty % of BL-Sv2 cells died within 2 days, whereas 50% cell death was not observed in the BL-bcl-2 cultures until 6 days had passed. Cross-linking of CD40 with a monoclonal antibody elevated Bcl-xL protein levels by 3 h and also provided a delay in CMB-induced death. Ninety-six h after the addition of 20 microM CMB, 78% of the BL-Sv2 cells were apoptotic, whereas ligation of CD40 on BL-Sv2 cells reduced the proportion of apoptotic cells to 38%. Overexpression of Bcl-2 (in BL-bcl-2 cells) reduced apoptosis to 41%. However, when the BL-bcl-2 cells were treated with CMB together with ligation of CD40, apoptosis was reduced further to only 17% at 96 h. The Bcl-2-mediated delay in the execution of CMB-induced apoptosis did not translate significantly to increased clonogenicity. In contrast, the provision of BL-Sv2 cells with an ability to interact with the adhesion molecule vascular cell adhesion molecule-1, CD40 ligation, and IL-4 significantly increased clonogenic survival, and this was improved in BL-bcl-2 cells exposed to these GC-derived signals. These data demonstrate that the kinetics of drug-induced apoptosis can be modulated by Bcl-2 as well as by IL-4, vascular cell adhesion molecule-1, and CD40 ligation, the latter possibly involving the function of Bcl-xL. That these factors appear to act together to enhance proliferative potential after DNA damage has important implications regarding the development of drug resistance in B-cell lymphomas and future strategies for improved chemotherapy.
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PMID:Germinal center-derived signals act with Bcl-2 to decrease apoptosis and increase clonogenicity of drug-treated human B lymphoma cells. 915 89

Ligation of CD40 inhibits apoptosis and stimulates proliferation of normal B cells, whereas ligation of CD95 (APO-1/Fas) induces apoptosis of activated lymphocytes. Aberrant signalling through the CD40 and CD95 antigens could thus participate in the pathogenesis of lymphoid malignancies. The expression and function of CD40 and CD95 on neoplastic B cells from patients with acute lymphoblastic leukaemia (ALL), chronic lymphocytic leukaemia (CLL) and non-Hodgkin's lymphoma (NHL) were examined. CD40 was expressed by all 30 B-cell tumours, whereas CD95 was detected on neoplastic B cells in only one of 10 cases of ALL, two of 10 cases of CLL, and three of 10 cases of NHL. Incubation with an agonistic CD95 monoclonal antibody (MoAb) did not augment apoptosis in any of the unstimulated B-cell neoplasms. CD40 triggering did not consistently inhibit spontaneous apoptosis, but ultimately stimulated the growth of neoplastic B cells in most cases. Furthermore, CD40 activation led to up-regulation of the CD95 antigen in all 30 B-cell neoplasms. Ligation of CD95 on CD40-activated tumour cells augmented apoptosis in five of 10 ALL, three of 10 CLL, and nine of 10 NHL cases. The degree of apoptosis induced by CD95 triggering was greater for NHL cells than for ALL cells or CLL cells. Bcl-2 expression by ALL and NHL cells was substantially decreased after in vitro culture, whereas Bcl-2 expression by CLL cells was not significantly changed. However, there was no correlation between the level of Bcl-2 expression and sensitivity to CD95-mediated apoptosis. Thus, factors other than levels of CD95 and Bcl-2 determine susceptibility of malignant B cells to apoptosis after CD95 triggering. CD40-activated lymphoma cells appear to be very sensitive to CD95-mediated apoptosis, suggesting potential strategies for treatment of NHL. Elucidation of the mechanisms underlying resistance of ALL and CLL cells to CD95 triggering may facilitate the development of novel therapeutic approaches to these diseases as well.
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PMID:Role of the CD40 and CD95 (APO-1/Fas) antigens in the apoptosis of human B-cell malignancies. 916 8

Whole-blood three-color immunofluorescence analysis was used to investigate the role of CD5/CD72 and CD21/CD23 receptor-ligand pair formation on B-chronic lymphocytic leukemia (B-CLL) cells as well as sCD23 and bcl-2 oncoprotein expression in disease progression and activity and total tumor mass in B-cell chronic leukemia (B-CLL) patients. Thirty-four patients with B-CLL and 19 controls were included in the study. The majority of B-cells in B-CLL patients coexpressed CD5 and CD72 as well as the CD23 antigen. Unlike B-cells in B-CLL patients, B-cells in all healthy controls tested had high expression of CD21 antigen. We identified two groups of B-CLL patients according to high (n = 20) or low levels (n = 14) of CD21 expression on CD19+CD23+ B-cells. Only in the patients with high CD21 expression, were sCD23 levels positively correlated with factors known to have prognostic significance in B-CLL (Rai stage and TTM) and could, therefore, be used as a prognostic parameter for these B-CLL patients. Bcl-2 oncoprotein expression did not differ between these patient groups. We presumed that in patients with a lower expression of CD21 antigen, the contribution of the CD21 molecule to homotypic adhesion was lacking. Further studies are necessary to determine the possible association of higher expression of the CD21 antigen with disease progression and the aggressive character of the B-CLL.
Leuk Lymphoma 1997 Apr
PMID:Phenotypic analysis of receptor-ligand pairs on B-cells in B-chronic lymphocytic leukemia. 916 40

An EBV(-) BL (Burkitt lymphoma) line (Black93), established from a patient exhibiting glucocorticoid-induced ATLS (acute tumor lysis syndrome), was highly sensitive to dexamethazone (DX) in vitro in the studies including 18 lymphoid cell lines (10 BL lines). In the BL lines, the highly sensitive ones always lacked Bcl-2(bcl-2 protein), while the DX resistant ones expressed Bcl-2. Black93 is the first BL cell-line derived from a ATLS patient, proving that cell lines can be established in vitro from ATLS patients. Since some pre-B ALL lines expressing Bcl-2 were DX-sensitive, the relationship between Bcl-2 and DX-sensitivity is not straight-forward. In the BL cells, however, the absence of Bcl-2 appears to be responsible for the DX-sensitivity. The DX-sensitivity and the absence of Bcl-2 is a major characteristic carried by t(8;14) neoplasms. In addition, there may be a stage of B-lineage differentiation without Bcl-2. While rare BL cases have been reported to express TdT (terminal desoxynucleotidyl transferase), Tree92 is the first such line, expressing S-Ig(mu, lambda), TdT and RAG (recombination activating gene)-1. When surface mu is ligated with antibody, RAG-1 was suppressed in expression, indicating that the signal through S-Ig can modulate the expression of RAG-1 in the Tree92 cells. Chromosome translocation is known to be associated with a specific stage of differentiation. Such specific stage for t(8;14), however, is broad enough to cover S-Ig(+), TdT(+) and RAG-1(+) stage, too. The phenotypic classification of leukemia/lymphoma and the delineation of differentiation scheme of normal hematopoietic cells, are dependent on each other. The documentation of the properties such as DX-sensitivity, the absence of Bcl-2, the expression of RAG-1 and its modulation by the signal through S-Ig is an example in which the diverse properties of human t(8;14) neoplasms can contribute for delineating the differentiation scheme of normal hematopoietic cells more precisely.
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PMID:Diverse properties of human t(8;14) neoplasms: [1] ATLS and absence of BCL-2 [2] modulation of RAG-1 expression with S-Ig ligation. 918 67

Bcl-2 over-expression has been shown to inhibit apoptosis induced by a variety of stimuli, whereas a predominance of Bax alpha to Bcl-2 accelerates apoptosis upon apoptotic stimuli. We sought to study the relevance of these apoptotic regulating gene products in leukaemia. In a panel of leukaemia and lymphoma cell lines (HL60, DoHH2, CEM C7, L1210 and S49), the Bax alpha-to-Bcl-2 ratio as assessed by Western-blot analysis correlated with sensitivity to dexamethasone treatment. In addition, in HAbax alpha-transfected CEM C7 clones, a similar correlation was found for dexamethasone and thapsigargin sensitivity. In bone-marrow aspirates from patients with childhood acute lymphoblastic or myelocytic leukaemia (ALL, n = 48; AML, n = 8), the Bcl-2 and Bax alpha levels were highly variable, but well within the range found in the Bax alpha transfectants and in the established cell lines. Bcl-2 levels were lower in T- than in B-lineage ALL, which could be ascribed to simultaneous inverse relation between Bcl-2 and WBC. By contrast, Bax alpha:Bcl-2 was independent of any presenting feature and was largely dependent on Bax alpha levels. Results suggest that Bax alpha:Bcl-2, rather than Bcl-2 alone is important for the survival of drug-induced apoptosis in leukemic cell lines and ALL.
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PMID:The Bax alpha:Bcl-2 ratio modulates the response to dexamethasone in leukaemic cells and is highly variable in childhood acute leukaemia. 918 97

Overexpression of the bcl-2 oncogene in the lymphoid compartment of transgenic mice prolongs the lifespan of lymphocytes and leads to a low incidence of lymphomas at later age. Transgenic mice carrying a mutated T-cell receptor lacking the variable domain (deltaV-TCRbeta) suffer from lymphocyte depletion and are highly predisposed to lymphoma development. We intercrossed Bcl-2-Ig and deltaV-TCRbeta transgenic mice to assess whether Bcl-2 could synergize with deltaV-TCRbeta in tumorigenesis as reported previously for other oncogenes. Surprisingly, bitransgenic deltaV-TCRbeta; bcl-2-Ig mice showed a reduction in the incidence of lymphomas. Analyses of prelymphomatous mice showed that Bcl-2 restored some of the phenotypic aberrations caused by the deltaV-TCRbeta transgene in the lymphoid compartment. The inhibitory activity of Bcl-2 on deltaVTCRbeta-induced lymphomagenesis was not observed when both transgenes were crossed into the RAG-1-/- background suggesting an important role for more mature lymphocytes in this phenomenon. These results show that, depending on the specific conditions, overexpression of Bcl-2 can both promote as well as impair lymphoma development.
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PMID:Bcl-2 reduces lymphomagenesis in deltaV-TCRbeta transgenic mice. 919 Oct 49

Bcl-2 is an oncogene that confers deregulated growth potential to B lymphocytes through its ability to inhibit apoptotic cell death. A specific molecular activity for the Bcl-2 protein has not been identified, but several lines of evidence have supported a role in protection of cells from oxidative stress. We investigated whether there is a correlation between expression of high levels of Bcl-2 and susceptibility of human Burkitt's lymphoma cell lines to H2O2-induced killing. The amount of H2O2 required to kill 50% of cells in 24 hours varied widely in the seven different lymphoma cell lines that were tested, ranging from 35 to 500 micromol/L H2O2. However, expression of high levels of endogenous Bcl-2 did not protect the cells from H2O2-induced killing, even though it was effective in protecting the cells from apoptosis induced by agents such as A23187. Thus, Bcl-2 was functional in preventing apoptosis but did not act in an antioxidant capacity. The results were confirmed using a Burkitt's lymphoma cell line overexpressing transfected bcl-2. The results may be explained by the observation that H2O2 was inefficient at inducing apoptosis in these mature B-cell lines. Nonapoptotic death induced by H2O2 was not prevented by Bcl-2.
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PMID:Bcl-2 does not protect Burkitt's lymphoma cells from oxidant-induced cell death. 919 72

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