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)

Diffuse large B-cell lymphomas (DLBCL) are a biologically and clinically heterogeneous entity. Although some DLBCL represent transformation of follicular lymphomas (FL), the proportion that is of follicular center cell (FCC) origin remains uncertain. Immunophenotypic and genotypic markers used to suggest a FCC origin for a lymphoma (bcl-6 and CD10 expression, lack of CD138 expression, bcl-2 rearrangements [R]) or to subdivide DLBCL (bcl-2 expression, bcl-6 R) were therefore investigated in 22 FL and 44 DLBCL using paraffin section immunostains and Southern blot/polymerase chain reaction analysis. All FL tested were bcl-6+ (19) and CD138- (22) with 16/19 also bcl-2 and CD10+ (classic phenotype), one bcl2+, CD10- (grade III) and two bcl2-, CD10+ (grade II or III). Bcl-2R was identified in 4/5 FL-GrI, 3/6 FL-GrII, and 1/3 FL-GrIII. Bcl-6R was found in 0/5, 2/4, and 0/3 FL, respectively. All but 3/41 DLBCL were bcl-6+ with 17/37 also bcl-2+ and CD10+. Three of these cases were also CD138+. Twelve bcl-6+ cases were bcl-2+, CD10-, six bcl-2-, CD10+, and two bcl-2-, CD10-. The three bcl-6- cases were bcl-2+, CD138- and two were CD10+. Bcl-2R was identified in 5/27 DLBCL with 4/5 bcl-2+, 3/4 tested CD10+ and 4/4 bcl-6+. Bcl-6R was identified in 7/26 including three with a classic FL phenotype. The vast majority of DLBCL in this study have an immunophenotype that supports a FCC origin. Although the proportion of DLBCL that co-expressed bcl-6, CD10 and bcl-2 was lower than for the FL, absence of bcl-2 or CD10 may be associated with higher grade FL It is also possible that bcl-6 expression is not completely specific for a FCC origin. Only a minority of cases suggested postfollicular differentiation. Only a minority of DLBCL show bcl-2R, suggesting that many have a different molecular pathogenesis than most low-grade FL. Bcl-6R did not exclude a FCC origin.
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PMID:Immunophenotypic and genotypic markers of follicular center cell neoplasia in diffuse large B-cell lymphomas. 1110 80

We examined 28 cases of primary bone lymphomas (PBL; stage IE) and 26 cases of systemic lymphomas involving the bone (SBL; stage IIE to IV). Two histologic types were prevalent: Diffuse large B-cell lymphomas (DLBCL; 26 PBL and 21 SBL) and CD30+ anaplastic large cell lymphomas (ALCL; 1 PBL and 4 SBL). A mature B phenotype (CD45+, CD20+, CD79a+, CDw75+/-, CD10-/+) was established in the DLBCL group. Bcl-2 immunoreactivity was demonstrated in 13/37 cases (35%), and bcl-6 immunostaining was observed in 22/32 cases (69%). ALCL showed null/T phenotype (CD3-/+; CD43+/-; CD30+), with ALK-1 expression in 3/3 cases. With use of a FR3A primer, a monoclonal pattern was demonstrated by PCR analysis in 22/41 lymphomas (54%). Bcl-2 translocation was identified in 2/41 cases (5%). This study details the clinical and pathological characteristics of bone lymphomas. Our immunohistochemical and molecular data suggest that most of them are "de novo" DLBCL and support their follicle center origin.
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PMID:Lymphomas of the bone: a pathological and clinical study of 54 cases. 1249 Sep 75

Diffuse large B-cell lymphoma (DLBCL) can be divided into prognostically important subgroups with germinal center B-cell-like (GCB), activated B-cell-like (ABC), and type 3 gene expression profiles using a cDNA microarray. Tissue microarray (TMA) blocks were created from 152 cases of DLBCL, 142 of which had been successfully evaluated by cDNA microarray (75 GCB, 41 ABC, and 26 type 3). Sections were stained with antibodies to CD10, bcl-6, MUM1, FOXP1, cyclin D2, and bcl-2. Expression of bcl-6 (P <.001) or CD10 (P =.019) was associated with better overall survival (OS), whereas expression of MUM1 (P =.009) or cyclin D2 (P <.001) was associated with worse OS. Cases were subclassified using CD10, bcl-6, and MUM1 expression, and 64 cases (42%) were considered GCB and 88 cases (58%) non-GCB. The 5-year OS for the GCB group was 76% compared with only 34% for the non-GCB group (P <.001), which is similar to that reported using the cDNA microarray. Bcl-2 and cyclin D2 were adverse predictors in the non-GCB group. In multivariate analysis, a high International Prognostic Index score (3-5) and the non-GCB phenotype were independent adverse predictors (P <.0001). In summary, immunostains can be used to determine the GCB and non-GCB subtypes of DLBCL and predict survival similar to the cDNA microarray.
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PMID:Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. 1450 78

Diffuse large B-cell lymphoma (DLBCL) can be divided into prognostically important categories such as germinal center B (GCB)-like and non-GCB-like groups. The t(14;18)(q32;q21) translocation defines a unique subset of DLBCL cases with a GCB gene expression profile. Two-color fluorescence in situ hybridization (FISH) analysis was applied to detect t(14;18) (q32;q21) in the nuclei of paraffin-embedded tissue sections from 61 patients with de novo DLBCL. Nine (15%) of 61 cases had a positive pattern. Fifty-seven cases were subclassified in an immunohistochemical study with anti-CD10, anti-bcl-6, and anti-MUM1 antibodies. In this classification, 21 cases (37%) were placed in the GCB group, and 36 (63%) were placed in the non-GCB group. There was a discrepancy between t(14;18) occurrence and bcl-2 protein expression. Bcl-2 protein expression was positive in 40 (67%) of 60 cases. The expression of bcl-2 protein in the GCB and non-GCB groups was not significantly different: 15 (71%) of 21 cases in the GCB group and 24 (67%) of 36 cases in the non-GCB group tested positive. We found no difference between the FISH-positive and FISH-negative groups in overall survival time (P = .6019, log-rank test). The overall survival rates of GCB and non-GCB groups did not differ significantly by immunohistochemical classification (P = .5399, log-rank test). Overall survival was significantly longer in the group with a low International Prognostic Index (IPI) score than in the group with a high IPI score (P = .0002, log-rank test). Our results suggest that immunohistochemical study and cytogenetic study with t(14;18) FISH cannot predict the clinical outcomes of DLBCL patients. A study with a larger number of patients may show a difference in clinical outcomes between FISH-positive and FISH-negative groups and between GCB and non-GCB groups.
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PMID:Incidence of diffuse large B-cell lymphoma of germinal center B-cell origin in whole diffuse large B-cell lymphoma: tissue fluorescence in situ hybridization using t(14;18) compared with immunohistochemistry. 1571 89

Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma with a 5-year survival rate of 35%-60%. Various clinical factors included in the International Prognostic Index have failed to identify the patients with DLBCL who will not benefit from the standard R-CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone plus rituximab) treatment regimen. Bcl-2 has been implicated in conferring resistance to chemotherapy in non-Hodgkin's lymphoma and is therefore a candidate prognostic marker in DLBCL. To identify the correlation between Bcl-2 expression and response to rituximab-containing treatment regimens, histologic materials were analyzed from 292 elderly patients with confirmed DLBCL. Of these, 155 patients had received R-CHOP (53%) and 137 had received CHOP (47%). One hundred ninety-three patients (66%) were found to express high levels of Bcl-2 protein in > 50% of the tumor cells. Of the 193 Bcl-2-positive patients, the patients who received R-CHOP had a better 5-year overall rate than patients treated with CHOP (56% vs. 42%; P = 0.01), whereas in the patients with Bcl-2-negative disease, there was no statistically significant difference in the 5-year overall survival rates between the R-CHOP and CHOP regimens (58% vs. 52%; P = 0.6). Therefore, the addition of rituximab to the standard chemotherapy regimen seems to have overcome the Bcl-2-associated resistance to chemotherapy.
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PMID:Bcl-2 gene expression as a predictor of outcome in diffuse large B-cell lymphoma. 1679 75

Diffuse large B-cell lymphoma (DLBCL) is a heterogenous entity. The pattern of CD15, CD30 and Bcl-2 expression is not well documented, especially in local population. We investigated 67 consecutive cases of DLBCL by immunohistochemistry on paraffin-embedded tissue. The male to female ratio was 1.2:1 with median age of 55 years, and more common nodal than extranodal in presentation. Only 3 of 67 cases expressed CD15. In addition, three cases showed weak membrane staining for CD30. Only one of these three cases was noted to have co-expression of CD15 and with occasional tumour cells showing weak CD30 expression. Bcl-2 protein was expressed in 43 of 67 (64%), more frequently in nodal than in extranodal tumours. In conclusion, CD15 and CD30 expressions are infrequent in DLBCL, and co-expression is rare. Bcl-2 protein expression is common in DLBCL.
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PMID:The pattern of CD15, CD30 and Bcl-2 expression in diffuse large B-cell lymphoma. 1724 18

In the last decades, considerable changes in the classification of lymphomas have been made. In addition to morphology and immunohistochemistry, the last WHO (2001) classification also utilizes cytogenetics and molecular biology. In many cases classification notices oncogenic mechanisms. The authors describe some differences in immunophenotype in certain entities: chronic lymphocytic leukaemia/small lymphocytic lymphoma--CLL/SLL, follicular lymphoma--FL, mantle cell lymphoma--MCL, diffuse large B-cell lymphoma--DLBCL, and anaplastic large cell lymphoma--ALCL, mainly with respect to prognosis. The authors point out to heterogeneity within the individual types of lymphomas from the point of view of morphology, immunohistochemistry and molecular biology. Recently it has been shown, that differences in prognosis are not limited to individual nosologic entities, but also may be found within the particular category of lymphoma. For example, CLL/SLL is divided in two different subunits according to mutational status of variable segment (VH) of the immunoglobulin heavy chain gene. The cases with unmutated VH segment display progressive disease which is in contrast to cases with the same morphology but with mutated VH segment. Similar differences were found in MCL. Attention is drawn to oncogenic and apoptosis-regulating mechanisms, such as gene p53 and the Bcl-2 family.
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PMID:[Non-Hodgkin's lymphomas (from Rappaport to WHO 2001 and nowadays). Review]. 1762 75

DLBCL (diffuse large B-cell lymphoma) is the most common subtype of non-Hodgkin's lymphoma. Current therapy for patients includes chemotherapy and monoclonal antibodies. Although oncogene-targeted therapy is dramatically successful for patients with certain kinds of leukaemias, there are no such agents yet for DLBCL. One reason for this is that several key oncogenes involved in DLBCL pathogenesis are transcription factors, which are difficult to therapeutically target with small molecules. Recent advances in the structural and functional characterization of DLBCL oncogenes have facilitated design of CPPs (cellpenetrating peptides) with potent inhibitory effects on DLBCL and other aggressive lymphomas. CPPs targeting the Bcl (B-cell lymphoma)-6, Bcl-2, Myc and NF-kappaB (nuclear factor kappaB) oncogenic pathways, among others, could improve efficacy and reduce toxicity of anti-lymphoma therapy. Another barrier towards effective therapy in DLBCL is its profound molecular heterogeneity. Combinatorial administration of oncogene-targeted CPPs based on the molecular profiles of individual patient tumours could allow individualized targeted therapy regimens to be developed.
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PMID:Targeting aggressive B-cell lymphomas with cell-penetrating peptides. 1763 52

Diffuse large B-cell lymphomas (DLBCL) display defects in cell cycle and apoptosis regulation. Therefore, the immunohistochemical expression patterns of the proteins p14, p21, Hdm2 and cyclin D2 were analyzed in relation to the previously reported expression of other major cell cycle proteins (p53, Rb, p16, p27, Ki-67 and cyclins A, B1, D2, D3 and E), apoptosis-associated proteins (bcl2, bcl-xl, bax, bak, bad and bid) and the B-cell differentiation immunophenotypes. Expression of the proteins p14, p21, Hdm2 and cyclin D2 was observed in 62/71 (87%), 22/76 (29%), 35/74 (47%) and 11/77 (14%) cases, respectively. Immunohistochemical alterations of the p53 (p53-Hdm2-p21-p14), Rb (Rb-p16-cyclin D [D2 or D3]) and p27 (p27-cyclin E) pathways were found in 56/77 (73%), 53/79 (67%) and 54/79 (68%) cases, respectively. Concomitant alterations of the p53-Rb, p53-p27 and Rb-p27 pathways were found in 40/77 (52%), 38/77 (50%) and 36/79 (46%) cases, respectively. Three concomitant alterations of the p53-Rb-p27 pathways were found in 28/79 (35%) cases. The main findings of the present study were the following: alterations of the p27 pathway were associated with higher expression of Ki-67 (p = 0.023); concomitant alterations of the p53Rb pathways and the p53-p27 pathways were associated with higher expression of cyclin A (p = 0.015 and p = 0.021, respectively) and concomitant alterations of the p53, Rb and p27 pathways were associated with higher expression of cyclin A (p = 0.013). Since cyclin A supports DNA replication, centrosome duplication and mitosis, these findings indicate that concomitant alterations of the p53, Rb and p27 pathways in DLBCL may have cooperative effects resulting in increased neoplastic cell proliferation. This might explain, at least partially, the association between concurrent aberrations of the p53, Rb and p27 pathways and aggressive clinical behavior in DLBCL.
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PMID:Alterations of the p53, Rb and p27 tumor suppressor pathways in diffuse large B-cell lymphomas. 1769 24

Diffuse large B-cell lymphoma (DLBCL) is a frequent lymphoma subtype with a heterogeneous behavior and a variable response to conventional chemotherapy. This clinical diversity is believed to reflect differences in the molecular pathways leading to lymphomagenesis. In this study, we have analyzed pretreatment, diagnostic samples from 108 DLBCL by immunohistology for expression of four markers linked to germinal center B-cells (CD10, Bcl-6), postgerminal center B-cells (MUM1) and apoptosis (Bcl-2). The results indicate that both CD10 and Bcl-6 are favorable prognostic indicators, in contrast to Bcl-2, which is an adverse parameter. Furthermore, using two algorithms for distinction between low- and high-risk patients proposed by Hans et al. (Blood, 2004; 103:275) and Muris et al. (Journal of Pathology, 2006; 208:714), it is shown that both are useful for predicting outcome in DLBCL. However, in this report, the algorithm of Hans et al. was superior to that of Muris et al. These findings confirm and extend other studies and indicate that different prognostic subgroups of DLBCL can be distinguished by simple immunohistological investigations for a limited number of markers. Whether these groups are also relevant for individual treatment decisions will be important to investigate in prospective studies.
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PMID:Profiling of diffuse large B-cell lymphoma by immunohistochemistry: identification of prognostic subgroups. 1798 9


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