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)

There is increasing evidence that bcl6 and CD10 expression may be related to apoptosis and cell cycle progression. Therefore, 79 cases of de novo diffuse large B-cell lymphomas were studied for the expression of bcl6 and CD10 proteins in relation to 1) the apoptotic index; 2) the proliferation-associated proteins Ki67, cyclin A, and cyclin B1; and 3) the expression of the bcl2, p53, Rb, p16, and p27 proteins. Expression of bcl6, CD10, and bcl2 proteins was found in 54/79 (68%), 28/79 (35%), and 47/74 (63%) cases, respectively. The bcl6/CD10 patterns were as follows: bcl6+/CD10+ (26 cases, 32%), bcl6+/CD10- (28 cases, 33%), bcl6-/CD10- (23 cases, 31%), and bcl6-/CD10+ (2 cases, 4%). Significant positive correlations were found between bcl6/Ki67 (r =.328, P =.003), bcl6/cyclin A (r =.265, P =.018), bcl6/apoptotic index (r =.327, P =.010), CD10/Ki67 (r =.296, P =.008), and CD10/apoptotic index (r =.397, P =.001). In addition, high expression of bcl6 showed significant correlation with negative (null/low) bcl2 expression (chi(2) test, P =.002). The above findings indicate that increased expression of the bcl6 and CD10 proteins is associated with increased apoptosis and proliferation in diffuse large B-cell lymphomas. The association between increased bcl6 expression and enhanced apoptosis might be due, at least in part, to the null/low bcl2 expression because previous in vitro data showed that bcl6 overexpression induces apoptosis accompanied by bcl2 and bcl-xl downregulation. Moreover, significant correlation was found between increased apoptotic index and the bcl6+/CD10+ pattern (t test: P =.014, Mann-Whitney test: P =.046). This finding and the positive correlation of the apoptotic index with bcl6 and CD10 expression may be related to previous results showing that the expression of these proteins has favorable effects on the clinical outcome of diffuse large B-cell lymphomas.
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PMID:Increased expression of the bcl6 and CD10 proteins is associated with increased apoptosis and proliferation in diffuse large B-cell lymphomas. 1274 54

Primary central nervous system lymphoma (PCNSL) is a rare disease. A small number of cytogenetic studies of PCNSL have been conducted and several reports have been published on associated molecular and protein expression data. We combined these approaches in a series of eight PCNSL cases, analyzing the chromosomal abnormalities using comparative genomic hybridization (CGH), testing for Epstein Barr virus (EBV) involvement by in situ hybridization for EBER, assessing expression of p53, Bcl-2, Bcl-6 and CD10 by means of immunohistochemistry, and screening for mutations of the TP53 gene by DGGE. TP53 gene mutations and EBV expression were not detected. Most of the cases showed p53, Bcl-6 and Bcl-2 protein expression. CGH revealed DNA copy number changes in all eight cases. The most frequent changes were gains of chromosome 12 (63%), chromosome 18 (50%) and 20q (38%), and loss of chromosome arm 6q (75%). No correlation between protein expression and chromosomal abnormalities was found in these eight cases. Although gains of chromosome 12, 18 and 20q and loss of 6q have also been reported in systemic diffuse large B-cell lymphomas, the frequency of 6q deletion is clearly higher in PCNSL. This creates a similarity to primary lymphomas of the testes that also frequently have deletions of 6q. This suggests that suppressor genes located on chromosome 6q may play a role in the development of lymphomas at immunoprivileged sites, like the CNS.
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PMID:Analysis of chromosomal copy number changes and oncoprotein expression in primary central nervous system lymphomas: frequent loss of chromosome arm 6q. 1280 86

Occasionally, primary large B-cell lymphomas (LBLs) arising in the spleen present with a micronodular pattern involving the splenic white pulp but sparing the red pulp. Histologically, the nodules contain scattered large B cells in a background of numerous T cells and histiocytes. They can cause substantial difficulty in histologic diagnosis as the morphology can mimic reactive and inflammatory lesions as well as other lymphoid neoplasms. In this study, we examined the histology and immunophenotype of the micronodular T-cell/histiocyte-rich LBL (MTLBL) of the spleen with a view to establish the characteristics that may be helpful in diagnosis. Paraffin-embedded material from 17 cases of MTLBL was studied. Clinical features and histology were reviewed and immunohistochemistry was performed for immunoglobulins, CD20, CD79a, CD3, CD68, CD10, BCL6, BCL2, OCT-2, epithelial membrane antigen, CD30, CD138, and EBV markers. The median age of presentation was 56 years, and the most frequent presenting features were anemia and B symptoms. All cases showed a micronodular pattern of involvement. The tumor nodules comprised a mixture of numerous CD3+ T cells and CD68+ histiocytes and scattered large CD20+ B cells with immunoglobulin light chain restriction. They were positive for BCL6 and OCT2 but negative for CD10, CD138, and EBV markers. There was variable expression of epithelial membrane antigen, Bcl-2, and CD30. No follicle dendritic cell meshwork infrastructure underlying the nodules could be demonstrated by staining for CD21 or CD35 antigens. The prognosis was poor; seven of the 12 cases with follow-up were dead within 2 years. MTLBL is unique variant of T-cell/histiocyte-rich diffuse LBL, characterized by primary splenic presentation and a micronodular architecture. The main differential diagnoses include granulomatous inflammation, Hodgkin's lymphoma, follicular lymphoma, and peripheral T-cell lymphomas.
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PMID:Micronodular T-cell/histiocyte-rich large B-cell lymphoma of the spleen: histology, immunophenotype, and differential diagnosis. 1282 82

Twenty-nine patients with diffuse large B-cell lymphomas presenting with bone involvement, including 18 localized primary bone lymphomas (group 1), 2 multifocal primary bone lymphomas (group 2), and 9 patients with extraskeletal disease at diagnosis (group 3), were studied. The tumors were subclassified according to the criteria of the WHO classification and evaluated by immunohistochemistry for expression of antigens associated with germinal center (GC) and non-GC stages of B-cell differentiation (bcl-6, CD10, MUM-1, VS38c, CD138, bcl-2, and CD44). The presence of a BCL-2/IgH gene rearrangement was investigated by polymerase chain reaction. All cases were characterized by similar clinicopathologic and morphologic features and had similarly good overall outcome. The patients (23 males, 6 females, median age 44 years) had tumors in long bones (14), axial skeleton (8), limb girdles (3), and multiple sites (4). Most tumors (24) were centroblastic, with multilobated cells in 12 cases. Almost half of the tumors (14 of 29, 48%) were bcl-6+CD10+ (GC-like), 9 of 29 cases (31%) were bcl-6+CD10- (indeterminate phenotype), and 6 of 29 cases (21%) were CD10-bcl-6- (post-GC like). The indeterminate phenotype was seen only in primary bone lymphoma. MUM-1 was frequently expressed in GC-like and non-GC-like categories. We found no evidence of plasmacytic differentiation by CD138, and VS38c immunoreactivity was distinctly rare (2 of 29 cases). CD44 was detected in 6 tumors, all CD10-. Bcl-2 was expressed by 70% of the tumors, but only 1 of 23 cases tested had a Bcl-2/JH rearrangement by polymerase chain reaction. A survival analysis showed that GC-like tumors had a longer overall survival duration compared with non-GC-like tumors (P = 0.0046). In conclusion, a GC-like immunophenotype characterizes roughly half of large B-cell lymphomas of bone and is associated with an improved survival.
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PMID:Diffuse large B-cell lymphoma of bone: an analysis of differentiation-associated antigens with clinical correlation. 1296 Aug 12

The appreciation of the role of apoptosis in the vast majority of diseases affecting humans has revolutionized the discovery and development of drugs targeting inflammation and oncology. Novel therapeutic approaches to modulate disease by regulating apoptosis are currently being tested in preclinical and clinical settings. Enthusiasm for some of these therapies is reflected in the fact that they have received U.S. Food and Drug Administration approval in record time. Approaches include the traditional use of small molecules to target specific players in the apoptosis cascade. They also include radical new approaches such as using antisense molecules to inhibit production of the Bcl-2 protein or antibodies that ligate either death receptors, such as TRAIL (tumour necrosis factor-related apoptosis-inducing ligand), or the MHC (HLA-DR), resulting in the initiation of apoptosis of target cells. Antibodies targeting cell-specific antigens are being used in conjunction with radioactive isotopes to deliver a more specific chemotherapy, particularly in the case of B-cell lymphomas. Other therapies target mitochondria, a key organelle in the apoptosis cascade. This diverse range of therapies includes photodynamic therapy, retinoic acid and arsenic trioxide, all of which induce apoptosis by generating reactive oxygen species. As our understanding of apoptosis increases, further opportunities will arise for tailor-made therapies that will result in improved clinical outcome without the devastating side effects of current interventions.
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PMID:Therapeutic approaches to the modulation of apoptosis. 1458 79

Bcl-2 protein expression has been associated with poor prognosis in patients with noncutaneous diffuse large B-cell lymphomas. In primary cutaneous large B-cell lymphomas, the location on the leg, the round-cell morphology defined as the predominance of centroblasts and immunoblasts over large centrocytes, and multiple skin lesions were identified as adverse prognostic factors. The prognostic value of bcl-2 protein expression has not been studied in large series of patients. We evaluated 80 primary cutaneous large B-cell lymphomas collected by the French Study Group on Cutaneous Lymphomas. The prognostic value of age, sex, number of lesions, cutaneous extent, location, serum lactate dehydrogenase (LDH) level, B symptoms, morphology, and bcl-2 protein expression was studied. The overall 5-year specific survival rate was 65%. In univariate analysis, advanced age, multiple skin lesions (n = 48), location on the leg (n = 25), round-cell morphology (n = 32), and bcl-2 expression (n = 39) were significantly related to death from lymphoma. In multivariate analysis, bcl-2 expression (P =.0003), multiple skin lesions (P =.004), and age remained independent prognostic factors. The 5-year specific survival rates in bcl-2-positive and bcl-2-negative patients were 41% and 89%, respectively (P <.0001). A new prognostic classification of primary cutaneous B-cell lymphoma should be based primarily on bcl-2 protein expression rather than the location of skin lesions.
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PMID:Bcl-2 protein expression is the strongest independent prognostic factor of survival in primary cutaneous large B-cell lymphomas. 1472

The aim of this study was to analyze the relations between differentiation immunophenotypes and the status of apoptosis and proliferation in diffuse large B-cell lymphomas. Therefore, the bcl6/CD10/MUM1/CD138 differentiation immunophenotypic profiles were studied in relation to (a) the apoptotic index, (b) the apoptosis-associated bcl2 family proteins bcl2, bcl-xl, bax, bak, bad and bid, (c) the proliferation index (Ki67) and (d) the cell cycle proteins cyclin A, cyclin B1, cyclin D3, cyclin E, p53, Rb, p16 and p27 in 79 cases of diffuse large B-cell lymphomas. Two major differentiation immunophenotypic profiles were distinguished: the germinal center B-cell-like profile; 31 cases (bcl6+/CD10+/-/MUM1-/CD138-: 29 cases and bcl6-/CD10+/MUM1-/CD138-: two cases) and the nongerminal center B-cell-like profile (bcl6+/-/CD10-/MUM1+/CD138-); 48 cases. The expression of bax, bak and bid and the apoptotic index were significantly higher in the germinal center B-cell-like profile than in the nongerminal center B-cell-like profile (P=0.045, 0.018, 0.003 and 0.034, respectively). In contrast, the expression of bcl-xl was significantly lower in the germinal center B-cell-like profile than in the nongerminal center B-cell-like profile (P=0.026). The expression of bcl6 and CD10 showed significant positive correlation with the expression of bax (r=0.659, P<0.001 and r=0.240, P=0.033, respectively), bak (r=0.391, P<0.001 and r=0.233, P=0.039, respectively) and bid (r=0.652, P<0.001 and r=0.238, P=0.035, respectively) and significant negative correlation with the expression of bcl-xl (r=-0.536, P<0.001 and r=-0.250, P=0.029, respectively). The expression of MUM1 showed significant negative correlation with the expression of bax (r=-0.276, P=0.014) and bid (r=-0.266, P=0.018) and significant positive correlation with the expression of bcl-xl (r=0.238, P=0.037). The above findings indicate that diffuse large B-cell lymphomas with germinal center B-cell-like immunophenotypic profile are associated with increased apoptosis status, high expression of the proapoptotic proteins bax, bak and bid and low expression of the antiapoptotic protein bcl-xl.
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PMID:Diffuse large B-cell lymphomas with germinal center B-cell-like differentiation immunophenotypic profile are associated with high apoptotic index, high expression of the proapoptotic proteins bax, bak and bid and low expression of the antiapoptotic protein bcl-xl. 1507 4

Overexpression of Bcl-2/Bcl-X(L) protein has been observed in more than 80% of B-cell lymphomas. Diffuse large cell lymphoma (DLCL) is the most common subtype of non-Hodgkin's lymphoma. (-)-Gossypol, a natural product isolated from cottonseeds, was discovered as a potent small-molecule inhibitor of Bcl-2 and Bcl-X(L) proteins, with a Ki value in the nanomole per liter range for both. In vitro, (-)-gossypol showed significant growth inhibition effect against WSU-DLCL2 lymphoma cell line and fresh cells obtained from a lymphoma patient with no effect on normal peripheral blood lymphocytes. As expected (-)-gossypol induced complete cytochrome c release from mitochondria, increased caspases-3 and -9 activity, and caused apoptotic death without affecting protein levels of Bcl-2, Bcl-X(L), Bax, and Bak. The addition of cyclophosphamide-Adriamycin-vincristine-prednisolone (CHOP) regimen to lymphoma cells preexposed to (-)-gossypol enhanced killing significantly. The maximum tolerated dose of (-)-gossypol in severe combined immunodeficient (SCID) mice was 40 mg/kg for three i.v. injections when given alone and 20 mg/kg x 3 when given in combination with CHOP. Using WSU-DLCL2-SCID mouse xenograft model, the tumor growth inhibition, the tumor growth delay, and the log10 kill of mice treated with (-)-gossypol + CHOP were better than CHOP or (-)-gossypol alone. We conclude that adding Bcl-2/Bcl-X(L) small-molecule inhibitor to standard chemotherapy may prove an effective strategy in lymphoma therapy.
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PMID:Preclinical studies of a nonpeptidic small-molecule inhibitor of Bcl-2 and Bcl-X(L) [(-)-gossypol] against diffuse large cell lymphoma. 1565 49

The formation of neoplastic B-cell follicles is accepted as a diagnostic criterion of follicular lymphoma. However, extranodal marginal-zone B-cell lymphomas (MZBLs) of mucosa-associated lymphoid tissue (MALT) type also sometimes contain numerous lymphoid follicles and may even have a predominantly follicular growth pattern. However, morphologic, immunohistochemical, and genotypic findings suggest that lymphoid follicles in extranodal MZBLs are neoplastic follicles formed as the result of colonization of previously reactive follicles by tumor cells (centrocyte-like cells). We present here 6 cases of nodal MZBL demonstrating a follicular growth pattern. Immunohistochemical study demonstrated that the tumor cells were CD10-, CD20+, CD79a+,CD138-, Bcl-2+, Bcl-6- and IRF4+. Residual nonneoplastic follicular center cells were CD10+, CD20+, CD79a+, Bcl-2-, and Bcl-6+. CD21/CD23 immunostain demonstrated a disrupted follicular dendritic cell pattern characteristic of follicular colonization in extranodal MZBL of MALT type. Taken in conjunction with the morphologic findings, nodal MZBL may also show a follicular growth pattern similar to extranodal MZBL of MALT type. The marginal-zone nature is most recognizable on immunohistochemistry, although the histologic appearance alone may cause some diagnostic problems. It is important for pathologists to consider this type of lesion in diagnostic practice.
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PMID:Follicular colonization of nodal marginal-zone B-cell lymphoma resembling follicular lymphoma: report of 6 cases. 1573 58

In contrast to nodal large B-cell lymphomas, recurrent chromosomal aberrations have been studied only in a small number of cases of primary cutaneous diffuse large B-cell lymphoma (PCDLBCL). We investigated 25 PCDLBCLs (classified according to the WHO-EORTC classification into PCDLBCL, leg-type, 8; and PCDLBCL, other, 17), using an interphase fluorescence in situ hybridization technique. All cases were analyzed for chromosomal aberrations commonly observed in nodal large B-cell lymphomas, including structural aberrations of the genes BCL2, BCL6, and c-MYC, and numerical aberrations of the chromosomes/genes 3, 7, 8, 11, 12, 13, 17, 18q, RB1, and p53. We observed genetic aberrations in 19 (76%) of 25 patients. The most frequent numerical aberrations were gains of chromosome 12 (7 of 25, 28%), 7 (5 of 25, 20%), 3 (5 of 25, 20%), 18q (3 of 25, 12%), 11 (3 of 25, 12%), X (3 of 25, 12%), and losses of chromosome/gene 17/p53 (3 of 25, 12%). BCL2, c-MYC, and BCL6 were rearranged with the IGH gene in 4 (16%), 1 (4%), and none (0%) of 25 cases, respectively. Most aberrations were homogeneously distributed among cases of PCDLBCL, leg-type and of PCDLBCL, other, cases located on the leg or at other body sites, cases with round and cleaved cell morphology, and Bcl-2+ and Bcl-2- cases. These results suggest that PCDLBCLs show similar chromosomal aberrations irrespective of classification, anatomic site, cell morphology, and Bcl-2 expression, and that many similarities between primary cutaneous and nodal diffuse large B-cell lymphomas can be observed.
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PMID:Genetic aberrations in primary cutaneous large B-cell lymphoma: a fluorescence in situ hybridization study of 25 cases. 1583 92


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