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)

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.
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PMID:Bcl-2 expression in acute myeloblastic leukaemia: relationship with autonomous growth and CD34 antigen expression. 915 52

Flow cytometric expression of bcl-2 protein was analyzed in 90 newly diagnosed acute myeloblastic leukemia (AML) patients using an anti-bcl-2 monoclonal antibody by direct immunofluorescence technique and results were correlated with FAB cytotype, CD34 expression and clinical outcome. Bcl-2 was expressed in all AML cases with different intensity. The mean fluorescence index (MFI), expressed as the ratio of sample mean channel:control mean channel, ranged from 3.0 to 39.5 with a median value of 14. The MFI was significantly higher (P = 0.01) in M0 (20.9) and M1 (18.3) than in M2 (11.7), M3 (12.4), M4 (11.8) and M5 (9.5) cytotypes. In addition, bcl-2 MFI significantly correlated both with CD34 positivity (P = 0.001) and with CD34 MFI (P = 0.01), being CD34 antigen expressed in 65% of patients with a bcl-2 MFI >14, and only in 35% of AML cases with a bcl-2 MFI >14. When bcl-2 intensity expression was correlated with complete remission (CR) rate, a higher MFI was associated with a low CR rate after standard intensive chemotherapy. In particular, CR was achieved in 86% of patients with a bcl-2 MFI <14, but only in 57% of patients with a MFI >14 (P = 0.008). A further decrease of CR rate to 41% was observed in patients in whom a higher bcl-2 MFI was coupled with the presence of CD34 antigen on their blasts. By statistical analysis we also demonstrated that both bcl-2 high MFI (>14) and CD34 expression are independent prognostic factors for achieving CR in AML. These data raise the hypothesis that high values of bcl-2 may confer on myeloid blasts a higher resistance to standard chemotherapy. However, identification of patients with high expression of bcl-2 may be important for a different therapeutic approach.
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PMID:High bcl-2 expression in acute myeloid leukemia cells correlates with CD34 positivity and complete remission rate. 944 23

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.
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PMID:Expression of lung resistance protein and correlation with other drug resistance proteins and outcome in myelodysplastic syndromes. 964 68

We performed flow cytometric analysis of CD34+ cell apoptosis in 59 patients with myelodysplastic syndrome (MDS) or acute myeloid leukaemia (AML) secondary to MDS (MDS-AML) using annexin V-FITC, which binds to exposed phosphatidylserine on apoptotic cells. Apoptosis was significantly increased in FAB subtypes RA, RARS and RAEB (<10% blasts) (56.5% (15.1-86.5%)) compared to normal controls (18.5% (3.4-33.4%), P<0.0001) and RAEB-t/MDS-AML (16% (2.1-43.2%), P<0.0001). There was no correlation between % apoptosis, Full blood count or cytogenetics in any disease category. Two-colour cytometric analysis of permeabilized CD34+ cells stained with antibodies to Bcl-2, Bcl-X (anti-apoptotic), Bax and Bad (pro-apoptotic), demonstrated significantly higher ratios of pro- v anti-apoptotic proteins in early MDS (2.47 (1.19-9.42) compared to advanced disease (1.14 (0.06-3.32), P=0.0001). Moreover, using repeated measures of variants (ANOVA), we found that variations between individual Bcl-2-related proteins differed significantly according to disease subtype (P<0.0005). Our results confirm that CD34+ cell apoptosis was significantly increased in MDS subtypes RA and RARS and fell with disease progression. Early MDS was also associated with a significantly higher CD34+ cell pro- v anti-apoptotic Bcl-2-family-protein ratio than advanced disease. Furthermore, patterns of expression of individual Bcl-2 related proteins differed significantly between different disease categories. However, no correlation between pro- v anti-apoptotic Bcl-2-family-protein ratios and the degree of apoptosis was observed.
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PMID:'Low-risk' myelodysplastic syndrome is associated with excessive apoptosis and an increased ratio of pro- versus anti-apoptotic bcl-2-related proteins. 988 23

Resistance to chemotherapy-induced apoptosis and a multidrug-resistance (MDR) phenotype, mainly mediated by P-glycoprotein (P-gp), contribute to chemotherapy failure in hematologic malignancies. To study apoptosis-regulating factors in acute myeloid leukemia (AML), we investigated cell samples of adults with de novo AML by flow cytometry for constitutive expression levels of the apoptosis-related molecules CD95 (n = 135), Bcl-2 (n = 131), and Bax (n = 66), as well as spontaneous apoptosis in vitro (n = 104) and susceptibility to anti-CD95-induced apoptosis (CD95 sensitivity) (n = 93). We correlated these findings with P-gp function as detected by the rhodamine123-efflux test (n = 121), immunophenotype, FAB morphology, cytogenetics, and clinical data of the examined patients. Immature FAB M0/1 AML cells expressed significantly more Bcl-2 (P < 0.0002) and less CD95 (P < 0.0003) compared with AML cells of the more mature FAB M2-5 subtypes. No maturation-dependent difference in Bax expression was observed. FAB M2-5 AML cells were more susceptible to anti-CD95-induced apoptosis (P < 0.008) and showed a lower P-gp function (P < 0.002) than FAB M0/1 AML cells. Leukemic cells of AML patients who achieved a complete remission (CR) after induction chemotherapy expressed less Bcl-2 than non-responder (NR) (69 CR, 23 NR; P = 0.05). CR was associated with a higher extent of spontaneous apoptosis in vitro (58 CR, 17 NR; P=0.05) and a tendency towards a higher CD95 expression (73 CR, 23 NR; P = 0.08) compared to NR. CR also correlated with a low P-gp function (70 CR, 21 NR; P = 0.008) and a tendency towards CD34 negativity (73 CR, 23 NR; P = 0.08). No correlation between Bax expression and response to induction chemotherapy (49 CR, 12 NR) was observed. In stepwise logistic regression analyses, P-gp function and the extent of spontaneous apoptosis in vitro as well as CD95 sensitivity but not Bcl-2, CD95, Bax, and CD34 expression levels emerged as significant markers for response to induction chemotherapy. We conclude that the constitutive expression of CD95 and Bcl-2, as well as CD95 sensitivity and P-gp function but not constitutive Bax expression depend on the maturation stage of leukemic cells in adult de novo AML. P-gp function, the extent of spontaneous apoptosis in vitro and CD95 sensitivity are more predictive for response to induction chemotherapy in adult de novoAML than the constitutive expression levels of the apoptosis-related molecules CD95, Bcl-2 and Bax.
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PMID:Clinical significance of CD95, Bcl-2 and Bax expression and CD95 function in adult de novo acute myeloid leukemia in context of P-glycoprotein function, maturation stage, and cytogenetics. 1060 14

It is generally accepted that the inhibition of apoptosis is one of the mechanism of drug resistance to tumor. Members of the bcl-2 gene family are the most important regulators in apoptosis. The purpose of this study is to evaluate the value of expression of bcl-2 and bax gene in predicting the prognosis of acute leukemia patients, and to explore the relationship between bcl-2 and bax expression and drug resistance. Seventy patients with acute leukemia entered this study. Expressions of bcl-2, bax and mdr-1 gene were measured by RT-PCR method and FCM. The result showed that: bcl-2 had been widely detected in specimens of blood or bone marrow from acute leukemia patients, the expression levels were much higher than those in normal control (1.46 vs 0.71, P < 0.05), bax expression levels and bax/bcl-2 ratio in patients had no significant difference with the control. No relationships were found between the expression levels of bcl-2 and bax and AL patients' age, sex, platelet counts, hemoglobin levels, percentage of marrow blasts, FAB classification, and S + G(2)M%. Both Bcl-2 protein expression (34.6% vs 69.2%, P < 0.03) and bax/bcl-2 mRNA ratio (37.1% vs 82.9%, P < 0.01) were associated with response to therapy and CR rate, bax/bcl-2 ratio also influences the overall survival time. There was no relationship between bcl-2 and bax expression levels and mdr-1 expression levels.
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PMID:[Clinic Significance of Expression of bcl-2 and bax Gene in Patients with Acute Leukemia and its Relationship with mdr-1 Gene Expression] 1257 66

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

Flow cytometric expression of Bcl-2 protein was analyzed in 67 newly diagnosed acute myeloblastic leukemia (AML) patients using an anti-Bcl-2 monoclonal antibody by direct immunofluorescence technique and result were correlated with FAB subtype, CD34 expression and clinical outcome. The number of Bcl-2+ cells in each sample was heterogenous (range, 19% to 96%), with mean of 81%. The percentage of Bcl-2+ cells was higher in M0 and M1 types according French-American-British classification. The mean fluorescence index (MFI), expressed as the ratio of sample channel: control mean channel was significantly higher (p < 0.01) in M0 (19.0) and M1 (17.6) than M4 (11.7) and M5 (8.9) cytotypes. In addition, Bcl-2 MFI significantly correlated both with CD34 positivity and with CD34 MFI. High percentage expression of Bcl-2 and MFI index of Bcl 2 was associated with a low complete remission rate after intensive chemotherapy (40.4% in cases with 20% and more positive cells vs 72% in cases with less than 20% positive cells). By statistical analysis we also demonstrated that both Bcl-2 high MFI (> 16) and CD34 expression are independent prognostic factors for achieving CR in AML.
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PMID:[Relation between Bcl-2 protein expression and results of therapy in patients with acute myeloblastic leukemia]. 1507 89

Apoptosis is the primary mechanism through which most chemotherapeutic agents induce tumor cell death. The balance in the expression of pro (Fas/CD95) and anti-apoptotic protein (Bcl-2) may control the response of leukemic cells to chemotherapy and subsequently affect the patient's prognosis. The aim of this study was to determine the levels of Bcl-2 and Fas expression on blast cells from patients with acute leukemia and to correlate the degree of expression to the clinical and laboratory prognostic factors and the patient's outcome. Forty newly diagnosed patients with acute leukemia (16 ALL, 24 AML) were included in the study. Ten normal subjects of matched age and sex were studied as a reference control group. The degree of Bcl-2 and Fas expression on acute leukemia blast cells were assessed before the start of therapy and on mononuclear cells after 1 year of follow up, using flow cytometry. The degree of Bcl-2 and Fas expression were significantly higher in AML (P<0.01,<0.05, respectively) and ALL (P<0.01, <0.05, respectively) as compared to controls. The expression of Fas and Bcl-2 was related to FAB type with the highest Bcl-2 and lowest Fas expression in M5 and T-ALL (P<0.01, for all). In ALL, patients responding to induction chemotherapy revealed lower Bcl-2 and higher Fas expression when compared to non-responders (P<0.05). In contrast, in AML the difference between responders and non-responders to induction chemotherapy regarding Bcl-2 and Fas expressions was not statistically significant (P>0.05). Bcl-2 and Fas expression were significantly elevated in the relapsed acute leukemia group (in both AML and ALL) when compared to those in remission (P<0.01, <0.05, respectively). Bcl-2 and Fas expression at diagnosis was not significantly different when those surviving were compared to the group who had died, either in the ALL or AML groups (P>0.05). Bcl-2 expression was significantly correlated to bone marrow blast cell counts (R=0.6, P<0.01), blast cell distribution ratio (R=0.4, P<0.05) and lymphadenopathy (R=0.33, P<0.05). Whereas Fas expression was significantly correlated to bone marrow blast cell counts (R=0.52, P<0.01). In conclusion, assessment of Bcl-2 and Fas expression at diagnosis in acute leukemia (1) could predict responsiveness to induction chemotherapy in ALL but not in AML group but (2) could not predict patients out come both in ALL and AML groups.
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PMID:Assessment of bcl-2 expression as modulator of fas mediated apoptosis in acute leukemia. 1520 66

To identify prognostic factors alternative or additional to drug-resistance and apoptosis proteins, we studied the impact of the expression of heat-shock proteins (HSPs) in 98 newly diagnosed acute myeloid leukemia (AML). HSP27 was expressed by 39%, HSP60 by 26%, HSP70 by 58%, HSP90 by 41%, and HSP110 by 30% of cases. HSP expressions were correlated with that of differentiation antigens (CD34, CD14, CD15, CD33) and that of drug-resistance (MRP, MRK) and apoptosis (Bcl-2) proteins. HSP90 and HSP110 were correlated with FAB subtype and karyotypic grouping. Complete remission (CR) was obtained in 68 cases (69%). Median disease-free survival (DFS) of the 68 remitters was 18.1 months with a 3-year DFS rate of 41%. CR rates were higher in patients with lower expression of HSPs. Overall survival (OS) was significantly longer in patients with lower expression of HSPs. Cytogenetics, CD34 positive expression, MRK positive expression, and HSP110 positive expression remained as pejorative prognostic factors for OS in the multivariate analysis. When considering patients with intermediate risk cytogenetics, HSP110 and MRP positive expressions and CD33 negative expression were of poor outcome, while HSP27 and HSP60 positive expressions appeared of pejorative prognostic value in patients with unfavorable karyotypes.
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PMID:Expression of heat-shock proteins is associated with major adverse prognostic factors in acute myeloid leukemia. 1603 31


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