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 inability to undergo apoptosis is a crucial mechanism of multidrug resistance in acute myeloid leukemia (AML), and the analysis of mitochondrial apoptotic proteins may represent a significant prognostic tool to predict outcome. Bcl-2 and Bax oncoproteins were evaluated in 255 de novo AML patients (pts) by flow cytometry using an anti-bcl-2 monoclonal antibody (MoAb) and an anti-bax MoAb. The results were expressed as an index (bax/bcl-2) obtained by dividing bax mean fluorescence intensity (MFI) and bcl-2 MFI. Lower bax/bcl-2 ratio was associated with French-American-British (FAB) M0-M1 classes (P =.000 01) and CD34 more than 20% (P <.000 01). There were striking inverse correlations between CD34 or CD117 MFI and bax/bcl-2 values (r = -.40, P <.000 001 and r = -.29, P =.000 002), confirming that immaturity is consistent with this index. Moreover, lower bax/bcl-2 levels were correlated with poor-risk cytogenetics (P =.0002). A significant higher complete remission (CR) rate was found in pts with higher bax/bcl-2 levels (79% versus 45%; P =.000 01). Also, both a longer overall survival (OS) and disease-free survival (DFS) were observed in pts with higher bax/bcl-2 levels (P =.000 01 and =.019). Noteworthy, bax/bcl-2 levels accurately predicted the clinical response and outcome of pts with normal or unknown cytogenetics. Indeed, within this subset of 147 pts, higher bax/bcl-2 ratio was significantly associated both with a higher CR rate (86% versus 42%; P <.000 01) and a longer OS (P =.0016). The independent prognostic value of bax/bcl-2 ratio was confirmed in multivariate analysis. Therefore, mitochondrial oncoproteins, such as bcl-2 and bax, represent both sensitive indicators of clinical outcome and potential targets of novel proapoptotic molecules in order to circumvent chemoresistance.
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PMID:Amount of spontaneous apoptosis detected by Bax/Bcl-2 ratio predicts outcome in acute myeloid leukemia (AML). 1242 99

The cell-surface expression and functional status of the CD95/Fas antigen on primitive hematopoietic progenitors isolated from human cord blood were studied. The CD34(+) cells freshly isolated from cord blood displayed low CD95 expression, combinations of cytokines such as SCF+FL upregulated the expression of CD95 in CD34(+) cells. Tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) further increased the CD95 expression induced by positive cytokines. The functional status of CD95-mediated apoptosis was analysed by incubation of CD34(+) cells in the presence of anti-CD95 monocloned antibody (McAb). The effect of anti-CD95 McAb was measured by viable cells counting, flow cytometry, LTC-IC and CFU-C assays. Viable cells and CFU-C numbers were 31.9 +/- 11.2 and 43 +/- 2.0 respectively, the rate of apoptosis was 42.9 +/- 12.4 in the presence of anti-CD95 McAb and TNF-alpha or IFN-gamma. However, growth factor deprivation or the early-acting cytokine such as SCF and FL cross-linking of CD95 lead to low apoptosis of CD34(+) cells. The correlation of increased intracytoplasmic levels of Bcl-2 and the presence of CD95 on surface of CD34(+) cells suggests that Bcl-2 may be involved in protecting against CD95-mediated apoptosis of cord blood CD34(+) cell.
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PMID:[Expression and function of CD95/fas antigen and Bcl-2 on cord blood hematopoietic progenitor cells]. 1251 29

There is increasing use of human umbilical cord blood (UCB) stem cells for unrelated donor transplantation. Successful engraftment depends in large measure on the dose and quality of cells in the UCB unit. In the present study, we attempted to identify a simple and rapid technique for assessing the quality and recovery of UCB cells following laboratory manipulation. Mononuclear cells (MNC) from fresh (<48 h old) and thawed UCB units were stained with 7-amino-actinomycin D (7-AAD), revealing 2-3% dead cells. The frequencies of apoptotic cells in fresh and thawed sample were similar. However, UCB held for 72 h showed higher levels of cell deterioration. Interestingly, staining with 7-AAD was more sensitive to cellular damage than was uptake of Trypan Blue. 7-AAD staining of MNC also correlated with retention of hematopoietic function (progenitor assays) such that 7-AAD staining frequencies <20% predicted maintenance of hematopoietic cells. Importantly, hematopoietic precursors were less susceptible to storage injury than were UCB MNC as a whole. MNC showed higher levels of 7-AAD staining and apoptosis than did CD34(+) cells. This observation was confirmed in studies of caspase-3 activation, where MNC consistently showed higher frequencies of activation than did CD34(+) cells, especially after overnight storage. Furthermore, antiapoptotic proteins Bcl-2 and Bcl-x were expressed more consistently in CD34(+) cells than in total MNC. In contrast, Bax levels increased with MNC apoptosis. In conclusion, the data suggest that 7-AAD staining of UCB MNC provides a rapid and simple technique for assessing the viability, recovery, and hematopoietic functionality of stored UCB.
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PMID:Assessment of cell viability and apoptosis in human umbilical cord blood following storage. 1266 42

Solitary fibrous tumor is a spindle cell tumor first described in the pleura, but also found in multiple extrathoracic sites including the meninges, orbit, nasal and paranasal sinuses. No cases have been previously reported in the cavernous sinus or pituitary fossa. We present the case of a 54-year-old woman who presented with progressive amaurosis. On imaging studies, a widely infiltrative lesion involving the pituitary fossa, sphenoid sinus, cavernous sinus, carotid artery, medial temporal, ethmoid, and pterygoid bones, and extending into the nasopharynx was discovered; impression was a malignant tumor originating in the pituitary fossa. At surgery, the tumor was only partially resectable because of extensive bony invasion and encasement of the carotid artery, and was found to compress but not invade the pituitary gland. Histology showed a spindle cell proliferation with a dense, hyalinized collagenous stroma and dilated vascular spaces, some showing a staghorn-like appearance. Areas of cellular pleomorphism and increased cellularity were present, but few mitoses were identified. Immunohistochemistry showed strong positivity with CD34, factor XIIIa, CD99, and Bcl-2. There was scattered cyclin D1, mib-1, and p53 positivity. Muscle, epithelial, vascular, and melanocytic markers were negative. These results led to the diagnosis of solitary fibrous tumor. The size, extensive invasion, and bony destruction indicated a tumor with at least low malignant potential. The occurrence of solitary fibrous tumors in the pituitary fossa and sinuses of the head and neck is rare, but must be considered in the differential diagnosis of spindle cell lesions in these regions.
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PMID:Widely invasive solitary fibrous tumor of the sphenoid sinus, cavernous sinus, and pituitary fossa. 1280 69

In order to observe the expression of Fas, FasL and Bcl-2 and apoptosis of bone marrow CD34(+) cells in patients with myelodysplastic syndrome (MDS), and to explore the relation between the expression of these antigens and apoptosis, the expression of Fas, FasL and Bcl-2 and apoptosis of bone marrow CD34(+) cell were evaluated by flow cytometry in 26 patients with MDS including 9 cases of refactory anemia (RA), 1 case of RA with ringed sideroblasts (RAS), 9 cases of RA with excess blasts (RAEB) and 7 cases of RAEB in transformation (RAEB-t), 10 patients with acute myeloid leukemia (AML) and 6 control patients with normal bone marrow. The results showed that the expression of Fas and FasL of CD34(+) cells significantly increased in all types of MDS patients compared with control group (P < 0.01). The expression of Bcl-2 on CD34(+) cells in RAEB and RAEB-t patients was much higher as compared with that in control group (P < 0.01), but there was no significant difference between RA/RAS patients and control group (P > 0.05). The expression rates of Fas on CD34(+) cells were almost identical in all kinds of MDS, but there was significant difference on the expression of Bcl-2 (RA/RAS < RAEB < RAEB-t). Apoptosis of CD34(+) cells significantly increased in RA/RAS and RAEB patients compared with control group (P < 0.01), but there was no difference between RAEB-t and control group. Moreover, apoptosis of CD34(+) cells in control much higher than that in AML group (P < 0.01). There was no correlation between the expression of Fas or FasL and apoptosis on CD34(+) cell of MDS patients. Nevertheless, there was a negative correlation between the expression of Bcl-2 and apoptosis. It is concluded that apoptosis of CD34(+) cells was affected by a lot of factors in MDS, in which Bcl-2 is an important factor of depressing apoptosis. During the progress from MDS to AML, apoptosis changes from overgoing to deficiency in CD34(+) cell.
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PMID:[Expression of Fas, FasL and Bcl-2 and apoptosis of bone marrow CD34+ cells in patients with myelodysplastic syndrome]. 1284 12

Hepatoblastoma, a childhood tumor of the liver, is composed of epithelial and mesenchymal elements in varying proportions and at various stages of differentiation. The epithelial element recapitulates the stages of hepatocyte development from the primitive blastema through embryonal hepatocytes to fetal hepatocytes. The blastemal or undifferentiated cells have been postulated to represent neoplastic hepatocyte progenitor cells. In this study, we examine the immunophenotype of the various epithelial cells of hepatoblastoma with special emphasis on the small undifferentiated cell component and compare it with that of adult hepatocytes and hepatic stem (oval) cells. Putative stem cells in the liver can express all of the following markers: alpha-feto protein, CK19 (OV-6), chromogranin A, Bcl-2, HepPar-1, and alpha1 microglobulin. The latter, like alpha-feto protein, is a plasma protein synthesized by hepatocytes. Both alpha1 microglobulin and HepPar-1 are expressed in fetal liver cells as early as 7 weeks of intrauterine life. They are also expressed in hepatocellular carcinoma and in hepatocytic cell lines derived from normal fetal or adult liver. Formalin-fixed, paraffin-embedded archival tissues from 10 predominantly epithelial hepatoblastomas were immunostained with antibodies directed against CD 34, alpha1 microglobulin, Bcl-2, HepPar 1, and CK19 using the avidin-biotin-peroxidase method. The undifferentiated small cell component did not express any of the markers studied, namely, Bcl-2, HepPar-1, alpha(1) microglobulin, CD34, or CK19. Hepatocyte-like cells were alpha1 microglobulin- and HepPar-1-positive, with the intensity of staining correlating with the degree of hepatocytic differentiation. Bcl-2 expression was restricted to areas of ductular differentiation. CK19 was detected in foci that showed duct formation. The small cells of hepatoblastoma did not express HepPar-1, Bcl-2, CK19, alpha1 microglobulin, or CD34, markers that characterize the immunophenotype of hepatic stem cells ("oval" cells). Thus, this observation raises the following questions: (1) is "hepatoblastoma" a misnomer? (2) is the expression of tumor antigens dysregulated in hepatoblastoma? (3) does the liver have two different types of progenitor cells, oval cells and blastemal cells, with differing immunophenotypes? and (4) do the blastemal cells, rather than oval cells, represent the more primitive progenitor cells of the liver?
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PMID:Small cells in hepatoblastoma lack "oval" cell phenotype. 1367 57

We present two cases of desmoplastic malignant mesothelioma (DMM) with pathological, immunohistochemical, and ultrastructural features. Each patient showed rapid progress and died within 1 year from appearance of the initial symptoms. Macroscopically, both showed a thickened pleura replaced by a tumor that encased the lung. Microscopic results of each showed that the tumors consisted of a dense fibrous area, with mild nuclear irregularities and hyperchromatism. In case 1, the tumor had invaded the diaphragm, chest wall, and cardiac sac; the mass in case 2 invaded the lung and diaphragm, and distal metastases were seen in the thoracic vertebrae, meninges, and liver. Ultrastructural findings in case 1 showed a few short blunt microvilli on the cell surfaces. DMM is occasionally difficult to distinguish from fibrous pleurisy and solitary fibrous tumor. Immunohistochemical examinations of the present cases showed the expression of cytokeratin and vimentin, and focal positive stainings of antihuman mesothelial cell antibody (HBME-1) in both, whereas CD34 and bcl2 were negative. Solitary fibrous tumor was excluded. Therefore, pathological, ultrastructural, and immunohistochemical findings led us a diagnosis of DMM in each case. The Ki-67 labeling index (Ki-67 LI) of cases 1 and 2 was 25.5 and 15.5, respectively, both high, which suggested malignancy. Widespread immunohistological panels of malignant mesothelioma were not evaluated; Immunohistological markers commonly used for the diagnosis of malignant mesothelioma were not evaluated; however, the high ki-67 LI results and positive HBME-1 staining were helpful factors for the diagnoses of DMM.
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PMID:Desmoplastic malignant mesothelioma: two cases and a literature review. 1450 61

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

In vitro studies demonstrating the induction of programmed cell death by cytotoxic drugs used in anticancer chemotherapy suggested that antileukemic treatment eliminates leukemia cells by apoptosis. We therefore analyzed apoptosis induction and activation of apoptosis signaling molecules in patients receiving remission induction treatment for AML and ALL during the initial phase of leukemia cell reduction. A coexistence of distinct populations of CD34(+) and CD34(-) leukemia cells could be identified. During chemotherapy, CD34(+) leukemia cells were more rapidly depleted than CD34(-) cells. Furthermore, a significant increase in leukemia cell apoptosis ex vivo was detected in CD34(+) cells, while no such increase was observed in the CD34(-) subpopulation, suggesting that CD34(+) leukemia cells are the main targets for apoptosis induction through antileukemic treatment. No alterations in Bax and Bcl-2 expression were found during in vivo chemotherapy, and CD95 expression and sensitivity remained low, indicating the induction of apoptosis independent of the CD95 system or regulation of protein levels of Bax and Bcl-2. The data suggest that analysis of leukemia cell subpopulations is required for further identification of apoptosis signaling molecules relevant for response to treatment and assessment of drug efficacy in vivo and in vitro.
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PMID:Apoptosis induction in peripheral leukemia cells by remission induction treatment in vivo: selective depletion and apoptosis in a CD34+ subpopulation of leukemia cells. 1452 71

Lack of apoptosis has been linked to prolonged survival of malignant B cells expressing bcl-2. The aim of the present study was to analyze the amount of bcl-2 protein expressed along normal human B-cell maturation and to establish the frequency of aberrant bcl-2 expression in B-cell malignancies. In normal bone marrow (n=11), bcl-2 expression obtained by quantitative multiparametric flow cytometry was highly variable: very low in both CD34(+) and CD34(-) B-cell precursors, high in mature B-lymphocytes and very high in plasma cells. Bcl-2 expression of mature B-lymphocytes from peripheral blood (n=10), spleen (n=8) and lymph node (n=5) was significantly higher (P<0.02) in CD23(-) as compared to CD23(+) B cells, independent of the type of tissue analyzed. Upon comparison with normal human B-cell maturation, bcl-2 expression in neoplastic B cells from 144 patients was found to be aberrant in 66% of the cases, usually corresponding to bcl-2 overexpression (63%). Follicular lymphoma (FL) carrying t(14;18) and MALT lymphoma were the only diagnostic groups constantly showing overexpression of bcl-2. Bcl-2 overexpression was also frequently found in precursor B-acute lymphoblastic leukemia (84%), typical (77%) and atypical (75%) B-cell chronic lymphocytic leukemia, prolymphocytic leukemia (two of three cases), mantle cell lymphoma (55%), but not in t(14;18)(-) FL, splenic marginal zone lymphoma, Burkitt lymphoma and multiple myeloma.
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PMID:Quantitative analysis of bcl-2 expression in normal and leukemic human B-cell differentiation. 1472 50


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