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)

Bcl-2 expression and its prognostic value were evaluated using the APAAP technique in 40 ALL patients. Because of a possible synergy between c-myc and bcl-2 proteins in cell lines, we compared 40 ALL of either T or B lineage with seven Burkitt's ALL or sporadic Burkitt's lymphomas (BL). We found the same high expression of bcl-2 in adult (Ad) and childhood (Ch) malignancies examined at presentation, regardless of the T or B phenotype. No bcl-2 expression was detectable in BL cases, except for two investigated at relapse. Bcl-2 staining intensity was also not related to the stage of blast differentiation, except in Ad T-ALL, or to the relapse rate. Ki-67, a marker of proliferation, was used to investigate the possible correlation between bcl-2 expression and the proliferative activity. An inverse correlation was found only in BL at presentation. We confirm that bcl-2 expression is the rule in ALL, regardless of the immunophenotypic characteristics at presentation, and that high expression is not correlated with a bad prognosis. Sporadic BL may represent a particular type of tumor, with bcl-2 expression in relapse, but not at presentation.
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PMID:High expression of bcl-2 is the rule in acute lymphoblastic leukemia, except in Burkitt subtype at presentation, and is not correlated with the prognosis. 806 Nov 3

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

Bcl-2 expression and its prognostic value were evaluated in 42 children with acute leukemia. The Bcl-2 expression of the leukemic blast cells was measured quantitatively by flow cytometry and was further analyzed by the simultaneous immunostaining of Bcl-2 with the surface membrane antigens, DNA, Ki-67 antigen. All of the cases showed a consistent expression of Bcl-2 protein; virtually all leukemic lymphoblasts were Bcl-2 positive. Although the expression of Bcl-2 varied widely from 7 to 80 x 10(3) MESF units, no significant difference was found in the mean value between the patients with acute lymphoblastic leukemia and those with acute myeloblastic leukemia. In more than half of the patients with AML, intraclonal heterogeneity of Bcl-2 expression was observed. The expression of Bcl-2 showed no apparent fluctuations during the different phases of the cell cycle. However, the proportion of Bcl-2-positive and -negative cells during the cell cycle was different between ALL and AML patients. In the ALL patients, few Bcl-2-negative cells were detected only in the GI phase, whereas in the AML patients Bcl-2-negative cells were detected in the S and G2/M phases, as well as in the G1 phase. No apparent difference was found in Bcl-2 expression between the Ki-67-negative noncycling population and the Ki-67-positive cycling population. Of the clinical features of these patients, only CD34 expression in the ALL patients was associated with high levels of Bcl-2 expression. In the 28 untreated cases of ALL, high expression of Bcl-2 was not an unfavorable factor for the outcome of this disease.
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PMID:Bcl-2 expression and prognosis in childhood acute leukemia. Children's Cancer and Leukemia Study Group. 959 36

The ratio of Bax to Bcl-2 protein can determine whether cells will die via apoptosis or be protected from it. Reh was found to express a high basal level of Bcl-2 but was lacking of Bax protein expression. Treatment with bryostatin 1 induced a down-regulation in Bcl-2 protein that was not accompanied by an obvious Bax protein induction or apoptosis. These results suggest that a decreased level of Bcl-2 alone in this cell line is not sufficient for apoptosis induction. In an effort to identify the mechanism whereby apoptosis could be induced in this ALL model, we treated Reh cells with three microtubule inhibitors: dolastatin 10, auristatin PE and vincristine, in the presence and absence of bryostatin 1. When used alone, only dolastatin 10 induced apoptosis that was detected morphologically, and by flow cytometry. Western blots revealed that dolastatin 10-induced apoptosis was accompanied by the induction of Bax protein and the reduction in Bcl-2 protein. Auristatin PE and vincristine induced both Bax and Bcl-2 protein, leaving the Bax:Bcl-2 ratio constant. Reh cells pretreated for 24 h with bryostatin 1 followed by dolastatin 10, auristatin PE or vincristine showed significant apoptosis which was accompanied by Bcl-2 protein down regulation and Bax protein up regulation. We conclude that: (1) expression of bax is necessary for apoptosis-induction in this model; (2) a decrease in Bcl-2 level alone is not sufficient and might not be necessary for apoptosis-induction; and (3) the ratio of Bax:Bcl-2 plays a critical role in susceptibility to apoptosis in Reh cells. The results from this study should prove useful in guiding the clinical application of these novel agents in the treatment of acute lymphoblastic leukemia.
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PMID:Bax:Bcl-2 ratio modulation by bryostatin 1 and novel antitubulin agents is important for susceptibility to drug induced apoptosis in the human early pre-B acute lymphoblastic leukemia cell line, Reh. 1057 32

We have examined the effects of antisense oligonucleotides to bcl-x on the survival and chemosensitivity of CEM cells, a T-acute lymphoblastic leukemia (T-ALL) cell line. Also, we have measured the levels of Bcl-2, Bcl-x, and Bax in 20 cases of T-ALL. By 18 h after the bcl-x antisense treatment, CEM cells showed over a 75% reduction in the levels of Bcl-xL protein and over 30% decreased viable cell counts compared with cells treated with the control oligonucleotide. The combination of bcl-x antisense plus either dexamethasone or doxorubicin showed either strong synergistic or additive killing of CEM cells, respectively. These findings indicate that bcl-x antisense has cytotoxic activity and increases chemotherapy-induced cell death in CEM cells, a model for T-ALL.
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PMID:Inhibition of Bcl-xL expression sensitizes T-cell acute lymphoblastic leukemia cells to chemotherapeutic drugs. 1179 21

We have analyzed by immunocytochemistry the p53 and Bcl-2 proteins expression in 49 patients with B-ALL, T-ALL and AML at the time of initial diagnosis. The diagnosis was based on morphologic and cytochemical criteria and on immunophenotyping. To demonstrate the p53 protein expression, p53 specific mouse antihuman immunoreagent clone DO-1 that recognizes both wild and mutated p53 protein was used. To detect Bcl-2 a monoclonal antibody that recognizes the 26-kD Bcl-2 protein was applied. For evaluation of both proteins a sensitive Immunotech detection kit based on peroxidase labeled streptavidin biotin reagent was utilized. The patients were divided according to the presence or absence of both, nuclear p53 and cytoplasmic Bcl-2 proteins. A relative low frequency of p53 protein expression in B- and T-lineage acute lymphoblastic leukemia has been shown at diagnosis. In AML cases, the frequency of p53 expression was higher than that in ALL. Bcl-2 protein immunoreactivity has been found in the majority of acute leukemia patients. The marked heterogeneity in the percentage of p53 and Bcl-2 positive cells in individual patients was observed. Comparative analysis of the distinct acute leukemia subtypes according to the percentage of p53 and Bcl-2 positive cells showed no significant differences except for p53 protein positivity in relation between T-ALL and AML cases. The samples from healthy subjects used as a control exhibited very low proportion of positively stained cells and significantly differed from p53 as well as Bcl-2 positive cases. p53 and Bcl-2 positivity have not been significantly affected neither by age, sex nor WB C counts. Association between myeloid cells maturation and proportion of p53 and Bcl-2 positive cells was observed. Noteworthy was the inverse relation between the higher proportion of p53 positive cells and low Bcl-2 positivity in some cases of acute leukemia. Although our preliminary results need to be confirmed in a larger group of patients, immunocytochemical analysis of p53 and Bcl-2 proteins, indicators of cell alterations, may help to identify risk patients requiring intensive therapy.
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PMID:Expression of p53 and bcl-2 proteins in acute leukemias: an immunocytochemical study. 1194 43

Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is an active constituent of Rheum palmatum, and showed inhibitory activity on lipopolysaccharide-induced NO production in our previous study. However, the apoptosis-inducing activity of emodin has remained undefined. Among three structurally related anthraquinones, including emodin, physcion, and chrysophanol, emodin showed the most potent cytotoxic effects on HL-60 cells, accompanied by the dose- and time-dependent appearance of characteristics of apoptosis including an increase in DNA ladder intensity, morphological changes, appearance of apoptotic bodies, and an increase in hypodiploid cells. Emodin at apoptosis-inducing concentrations causes rapid and transient induction of caspase 3/CPP32 activity, but not caspase 1 activity, according to cleavage of caspase 3 substrates poly(ADP-ribose) polymerase and D4-GDI proteins, the appearance of cleaved caspase 3 fragments being detected in emodin- but not physcion- or chrysophanol-treated HL-60 cells. A decrease in the anti-apoptotic protein, Mcl-1, was detected in emodin-treated HL-60 cells, whereas other Bcl-2 family proteins including Bax, Bcl-2, Bcl-XL, and Bad remained unchanged. The caspase 3 inhibitor, Ac-DEVD-CHO, but not the caspase 1 inhibitor, Ac-YVAD-CHO, attenuated emodin-induced DNA ladders, associated with the blockage of PARP and D4-GDI cleavage. Free radical scavenging agents including NAC, catalase, SOD, ALL, DPI, L-NAME and PDTC showed no preventive effect on emodin-induced apoptotic responses, whereas NAC, CAT and PDTC prevented HL-60 cells from ROS (H(2)O(2))-induced apoptosis through inhibition of caspase 3 cascades. Induction of catalase, but not SOD, activity was detected in emodin-treated HL-60 cells by in gel activity assays, and H(2)O(2)-induced intracellular peroxide level was significantly reduced by prior treatment of emodin in HL-60 cells. Our experiments provide evidence that emodin is an effective apoptosis inducer in HL-60 cells through activation of the caspase 3 cascade, but that it is independent of ROS production.
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PMID:Emodin induces apoptosis in human promyeloleukemic HL-60 cells accompanied by activation of caspase 3 cascade but independent of reactive oxygen species production. 1244 60

To explore Bcl-2 and P53 gene proteins expression on human leukemia cells and their relationship with chemotherapeutic efficacy, Bcl-2 and P53 gene proteins expression was assayed by ABC immunohistochemical staining. Results showed that the expression rates of Bcl-2 and P53 gene proteins were 67% and 41% respectively in leukemia cells from 52 patients. While there was no difference of Bcl-2 protein level in ALL and ANLL, the P53 protein level was higher in ANLL than that in ALL (P < 0.05). When CML patients got into the blast crisis phase, the level of Bcl-2 and P53 proteins became very high. Compare with previously untreated AL, relapse/refractory AL patients had higher Bcl-2 and P53 protein level, lower marrow complete remission, and was easy to relapse. The expression of Bcl-2 and P53 protein could be used as new predictors of chemotherapeutic efficacy and prognosis in patients with leukemia. The high protein expression of Bcl-2 and P53 demonstrated that CML was conversion to blast crisis phase.
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PMID:[Expression of Bcl-2 and P53 Gene Proteins on Leukemia Cells and Its Correlation with Chemotherapeutic Efficacy] 1257 96

The majority of follicular lymphoma and Burkitt's lymphoma are associated with reciprocal translocations involving BCL2 and cMYC, respectively. Unusual reports of aggressive lymphoma presenting with both translocations have been described as well as rare cases with a third structural alteration usually involving BCL6. The patient described here presented with aggressive high-grade lymphocytic leukemia, FAB subtype L2 (ALL-L2), and three reciprocal translocations, t(14;18)(q32;q21), t(8;14)(q24.1;q32), and t(1;2) (q22-23;p13). Despite immature morphology the leukemic blasts had a mature B-cell phenotype; they were positive for surface immunoglobulin heavy chains and negative for CD34, TdT, and CD10. Most reported dual t(14;18)/t(8;14) cases have not shown sIg and were positive for CD10. Molecular genetic analyses showed the typical rearrangements of BCL2 and cMYC as well as the FCGR2B gene on chromosome 1q23. The occurrence of a third oncogene rearrangement in association with the dual BCL2, cMYC translocations in ALL patients is very rare. To our knowledge, this is the first case where the third hit involves the FCGR2B locus. This report reiterates the poor prognosis associated with activation of cMYC together with elevated Bcl-2 expression. These data also support recent evidence that dysregulation of FCGR2B may play a role in tumor progression.
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PMID:Case of acute lymphoblastic leukemia presenting with t(14;18)/BCL2, t(8;14)/cMYC, and t(1;2)/FCGR2B. 1450 97

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