Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:A9QXG9 (bcl-2)
 7,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The long median survival time of patients with follicular non-Hodgkin's lymphoma (NHL), means that the efficacy of new treatments are difficult to assess in the short term. Bcl-2 is an inhibitor of apoptosis and overexpression of the bcl-2 gene in the blood or bone marrow is a feature in up to 85% of patients with follicular NHL. Levels of bcl-2(+) cells in the peripheral blood or bone marrow therefore are a useful measure of disease status in such patients and can be detected by polymerase chain reaction (PCR). Complete bcl-2 clearance from the bone marrow (molecular remission) following autologous stem cell transplant (ASCT) for follicular NHL is considered to be an important prognostic factor for disease-free survival. Tumour cell contamination of the stem cell grafts used in ASCT is commonly associated with relapse. This can be addressed by purging the stem cell harvest prior to transplantation. Various methods of in vitro purging after stem cell collection have been shown to reduce the level of contamination but yield is invariably reduced and grafts remain bcl-2 positive. However, in vivo purging with rituximab during the process of collection has been used to obtain bcl-2-negative stem cell harvests without compromising the yield. Rituximab is a monoclonal antibody licensed for treatment of relapsed and refractory low-grade or follicular NHL. Rituximab targets the CD20 antigen, which is found on cells of the B cell lineage. When used for in vivo purging it depletes the peripheral blood of CD20-positive cells and prevents contamination by lymphoma cells. Molecular remission, as measured by bone-marrow bcl-2 clearance, has been achieved in 7/7 patients with follicular NHL at 1 year after treatment with ASCT using rituximab as an 'in vivopurse', followed by rituximab maintenance. Early clinical outcomes are also encouraging.
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PMID:Bcl-2 clearance: optimising outcomes in follicular non-Hodgkin's lymphoma. 1184 Jan 56

Follicular lymphoma is a rare lymphoid malignancy in pediatric patients and consequently remains poorly characterized, particularly with respect to its immunophenotype and molecular pathogenesis. A total of 23 pediatric patients with follicular lymphoma were identified, with a median age of 11 years and a male-to-female ratio of 2.3:1. Of the 19 patients for whom presenting clinical features were available, 15 patients had stage I, 1 had stage II, and 3 had stage III or IV disease. All tumors had a follicular architecture, and 74% of cases had grade 2 or 3 histologic features. All patients expressed CD20 and bcl-6, and 80% were positive for CD10. Bcl-2 expression was detected in only 5 of 16 cases. Consistent with this finding, bcl-2 gene rearrangements were detected in only 2 of 16 cases by polymerase chain reaction. These patients were treated primarily with cyclophosphamide, doxorubicin, vincristine, and prednisone-based chemotherapy; 4 patients also received involved-field irradiation. Of the 13 patients with available clinical follow-up, all but 2 achieved durable clinical remission. Importantly, all 4 patients with tumors diffusely positive for bcl-2 either presented with stage III/IV disease or had disease refractory to therapy, whereas patients with bcl-2-negative tumors uniformly had stage I disease, achieved complete remission, and experienced no relapses. These findings indicate that, in contrast to adult follicular lymphomas, dysregulated bcl-2 expression does not play a significant pathogenetic role in most pediatric follicular lymphomas. However, bcl-2 expression in pediatric follicular lymphoma identifies a subset of patients in whom disease is often disseminated at clinical presentation and is more refractory to combination chemotherapy.
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PMID:Clinicopathologic analysis of follicular lymphoma occurring in children. 1187 66

Body cavity-based lymphomas are fluid-based lymphomas that are not associated with a tumor mass or adenopathy which could explain the origin of the lymphomatous effusion. A distinct lymphoma that grows in the body cavity as a lymphomatous effusion in the absence of a tumor mass has been identified as a primary effusion lymphoma. This almost exclusively occurs in patients with acquired immunodeficiency syndrome (AIDS), who invariably have a history of Kaposi sarcoma. We report a rare case of a recurrent pleural effusion in an immunocompetent patient. There was no evidence of lymphadenopathy or an associated mass on computerized tomography of the chest, abdomen and pelvis. Serology for HIV, HHS-8, EBV and HTLV-1 were negative. Cytologic examination of the pleural fluid showed an elevated white cell count with 97% lymphocytes, mostly with T-cell markers. Bone marrow aspirate and biopsy were negative and bronchoscopy was unrevealing. Pleural biopsy was significant for >70% T-lymphocytes and some large atypical cells. Which had CD19, CD20 and weak bcl-2 positivity. Kappa and lambda light chains did not show distinct clonality. A preliminary diagnosis of T-cell rich B-cell lymphoma (TCRBCL) of the pleural cavity was made. The diagnosis was confirmed with DNA studies done on the pleural biopsy specimen using PCR and southern blot. Dual rearrangement of Ig heavy chain region and TCR-beta genes were identified. The patient responded to combination chemotherapy with cyclophosphamide, adriamycin, vincristine and prednisone. Our case is the first known case of pleural cavity-based TCRBCL and illustrates the role of gene rearrangement studies in such patients.
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PMID:Immunoglobulin and T-cell receptor gene-gene rearrangement in pleural cavity-based T-cell rich B-cell lymphoma in an immunocompetent patient. 1190 29

Primary cutaneous diffuse large B-cell lymphoma (DLBCL) is an uncommon lymphoma. Some authors have suggested that large B-cell lymphoma can be segregated based on anatomic site, with tumors of the lower extremity being unique. We report 15 cases of primary cutaneous DLBCL. Each case was analyzed immunohistochemically using antibodies specific for CD3, CD5, CD10, CD20, bcl-2, bcl-6, and p53. Polymerase chain reaction analysis for t(14;18)(q32;q21) also was performed. There were 13 men and 2 women (median age, 64 years). Thirteen tumors were composed predominantly of centroblasts, and 2 were immunoblastic. There was a median follow-up of 72 months. Of the 4 patients with primary cutaneous DLBCL of the lower extremity (thigh, knee, leg), 2 (50%) experienced a recurrence and 1 patient died of disease. In the non-lower extremity cases, 18% (2/11) recurred and no patients died of disease. We conclude that primary cutaneous DLBCL usually occurs in elderly patients with a male predominance. Recurrences are common, but death of disease is rare.
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PMID:Primary cutaneous diffuse large B-cell lymphoma: a clinicopathologic study of 15 cases. 1193 32

We used a panel of paraffin antibodies to determine whether neoplastic and nonneoplastic lymphoid aggregates in the bone marrow can be distinguished reliably. Formalin-fixed, paraffin-embedded bone marrow core biopsy specimens with lymphoid aggregates were stained using primary antibodies directed against bcl-2, bcl-6, CD5, CD10, CD20, and CD23. We studied 61 cases (26 follicular lymphoma and 35 benign or atypical aggregates). We found that no single stain is sufficient for identification of neoplastic lymphoid aggregates. However, this distinction was made possible by using a panel of antibodies. Under the conditions we tested, the most useful antibodies were CD10, bcl-2, CD5, and CD20. Most benign or atypical aggregates do not express CD10 and CD23. In addition, nonneoplastic aggregates had a large population of T cells. bcl-2 was useful in an architectural context for distinguishing neoplastic aggregates. bcl-6 often was expressed in both neoplastic and nonneoplastic aggregates and, thus, poorly discriminated between these processes. We studied the expression of CD10 and bcl-6 in selected lymph nodes in some cases.
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PMID:The usefulness of immunohistochemistry in the diagnosis of follicular lymphoma in bone marrow biopsy specimens. 1193 40

The t(14;18) is the most frequent chromosomal aberration observed in follicular lymphoma (FL), and is less frequent in diffuse large cell lymphoma (DLCL). The bcl-2/IgH rearrangement constitutes good target for polymerase chain reaction (PCR) detection that allows to find out one tumor cell in 100,000 normal cells. The PCR assay was used to detect bcl-2-rearranged cells in blood and bone marrow (BM) in 63 previously untreated patients with DLCL and in 53 patients with FL. Twenty five FL patients (47%) and 9 DLCL patients (14%) had PCR-detectable lymphoma cells in BM and peripheral blood. Minimal residual disease (MRD) was evaluated in 17 FL and 5 DLCL patients undergoing first-line chemotherapy. Three DLCL patients (60%) but only 1 FL (6%) patient achieved molecular response (PCR-negative status in BM). Two PCR bcl-2/IgH positive patients with FL were treated with rituximab (anti-CD20 antibody) and had no PCR-detectable lymphoma cells in BM after the therapy. Peripheral blood stem cells (PBSC) were harvested in 5 FL (1 PCR-negative) and in 2 DLCL (1 PCR-negative) patients. PCR-positive lymphoma cells contamined PBSC in all patients with BM PCR-positivity before harvesting. Five FL patients underwent autologous transplantation (AT). No bcl-2/IgH positive cells were detected in 4 patients (80%) at any point after AT. One patient achieved molecular response after rituximab treatment. All the patients are in CR 6, 22, 30, 31 and 42 months respectively, after AT. On the other hand, 4 FL patients in clinical complete remission, but with persistent PCR positivity in BM relapsed with median of 21 months (interval, 14-28 months) from the end of a first-line chemotherapy. Thus, the results show that PCR detection of the bcl-2/IgH rearrangement is a very useful method in evaluating the BM infiltration by lymphoma cells especially in the situation of MRD. Conventional chemotherapy did not eradicate bcl-2 positive cells in BM in most of lymphoma patients, but autologous transplantation or rituximab immunotherapy can induce molecular response in a significant proportion of them. Our results support the previous observations of the molecular response importance in view of better disease free and probably also overall survival.
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PMID:Polymerase chain reaction detection of cells carrying t(14;18) in bone marrow of patients with follicular and diffuse large B-cell lymphoma: the importance of analysis at diagnosis and significance of long-term follow-up. 1194 45

Follicular lymphoma and mantle cell lymphoma are incurable with standard chemotherapy regimens. One approach to improve outcome in patients with these diseases is high-dose therapy and autologous stem cell transplantation. Rituximab, an anti-CD20 monoclonal antibody, is specific for the B-cell surface antigen and can be used in autologous stem cell transplantation to eliminate lymphoma cells before the harvest (in vivo purging) or to prevent regrowth of malignant cells following transplant (post-transplant therapy). Preliminary data from an ongoing multicenter study evaluating the safety and efficacy of rituximab as a post-transplant consolidation therapy in patients with follicular lymphoma and mantle cell lymphoma are presented. After high-dose therapy and autologous stem cell transplantation together with rituximab treatment, 92% of patients are in complete remission at the 18-month study follow-up, suggesting that rituximab is a valuable and potentially curative treatment for patients with follicular lymphoma and mantle cell lymphoma. Six months after treatment, all evaluable patients became polymerase chain reaction-negative for the bcl-1 and bcl-2 chromosomal rearrangements and remained so during follow-up, indicating that rituximab is able to eliminate minimal residual disease and bring about high rates of durable remissions in these patients.
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PMID:Improving outcomes in transplantation. 1204 May 31

To analyze the relationship between immunophenotyping profile and main clinicopathological features and outcome in diffuse large B-cell lymphoma (DLBCL), we studied 128 patients (59 men, 69 women; median age 65 years) consecutively diagnosed with de novo DLBCL in a single institution. Cells from each patient were immunostained with CD20, CD79a, CD5, CD10, bcl-6, MUM1, CD138, bcl-2, p53, p27, and Ki-67 antibodies. Four immunophenotyping profiles were distinguished according to the pattern of differentiation: germinal center-CD10(+) (GC-CD10(+); CD10(+)/Bcl-6(+)/MUM1(-)/CD138(-)), germinal center-CD10(-) (GC-CD10(-); CD10(-)/Bcl-6(+)/ MUM1(-)/CD138(-)), post-germinal center (pGC; CD10(-)/bcl-6(+/-)/ MUM1(+)/CD138(-)), and plasmablastic (CD10(-)/bcl-6(-)/MUM1(+)/CD138(+)). Rearrangement of bcl-2 was studied by polymerase chain reaction (PCR) in 57 patients. Single-antigen expression was as follows: CD5, 2%; CD10, 21%; bcl-6, 72%; MUM1, 54%; CD138, 2%; bcl-2, 59%; p53, 28%; p27, 40%. Distribution according to differentiation profiles was as follows: GC-CD10(+), 24 patients, GC-CD10-, 30 patients; pGC, 60 patients; plasmablastic, 2 patients; other patterns, 12 patients. The pGC profile was associated with primary nodal presentation and immunoblastic morphology, whereas GC-CD10(+) tumors showed disseminated disease, centroblastic morphology, bcl-2 rearrangement, and lower Ki-67 proliferative index. GC-CD10(-) patients more often presented with primary extranodal origin, early stage, normal lactic acid dehydrogenase (LDH) levels, and low or low/intermediate International Prognostic Index (IPI) scores than the others. However, no significant difference was found in terms of response or overall survival (OS) according to these profiles. Expression of bcl-2 was associated with advanced stage, high or high-intermediate IPI, and poor OS. Expression of bcl-2 maintained predictive value in multivariate analysis, with stage and LDH. In conclusion, differentiation profile was associated with particular clinicopathological features but was not essential to predicting outcome in DLBCL patients.
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PMID:Clinical impact of the differentiation profile assessed by immunophenotyping in patients with diffuse large B-cell lymphoma. 1239 66

The incidence of B-cell non-Hodgkin lymphomas (B-NHL) at nodal and extranodal sites is fairly different. Follicular lymphomas (FL) occur predominantly at nodal sites and rarely in the gastrointestinal tract, while marginal zone lymphomas (MZL) of the mucosa-associated lymphatic tissue (MALT) type predominate in the digestive organs and especially in the stomach. We report a 72-year-old female patient admitted for gastroscopy because of epigastric pain. The antral biopsies showed dense lymphocytic infiltrates, partially forming follicles with widened marginal zones and monocytoid cells. Multiple lymphoepithelial lesions (LEL) were also observed. A MZL of the MALT type was suspected morphologically. Immunohistochemical analysis revealed the lymphatic infiltrates to be CD20, bcl-2, bcl-6 and CD10 positive, and negative for CD43, CD5 and cyclin D1. PCR-based analysis showed a JH/bcl-2 rearrangement, corresponding to the translocation t(14;18). An extranodal FL mimicking MZL was diagnosed. The present case is remarkable, as it demonstrates that the detection of LEL and monocytoid B-cells, although suggestive for MZL, is not entirely specific and can also be observed in FL. Pathologists should be aware of this diagnostic pitfall in classifying gastric B-NHL. In equivocal cases, a careful morphological examination, supported by specific immunohistochemical and molecular findings, should lead to the correct diagnosis.
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PMID:Primary gastric follicular lymphoma with parafollicular monocytoid B-cells and lymphoepithelial lesions, mimicking extranodal marginal zone lymphoma of MALT. 1246 20

The purpose of this chapter is to review the available information on the use of high-dose treatment (HDT) in large B-cell, follicular and mantle-cell lymphoma. The last 10 years have seen a dramatic increase in the number of patients receiving high-dose treatment with autologous haemopoietic progenitor cell support for non-Hodgkin's lymphoma. In patients with recurrent large B-cell lymphoma, HDT is now accepted as the 'standard of care', provided responsiveness to conventional chemotherapy at the time of recurrence has been demonstrated. In contrast, the situation in newly diagnosed patients is far from clear. Several phase III studies have been conducted, comparing conventional chemotherapy with either: the same treatment followed by HDT or an abbreviated number of cycles of conventional therapy followed by HDT. The results hitherto have not conclusively shown an advantage for HDT. In mantle-cell and follicular lymphoma, HDT should still be regarded as experimental. Current studies are evaluating the use of anti-CD20, given either as part of the treatment prior to HDT or as maintenance therapy. In view of the propensity for both of these illnesses to involve the bone marrow, a number of studies have addressed the question of in vitro treatment of the stem cell product. The advent of PCR analysis has made it possible to evaluate the significance of 'molecular remission'. In follicular lymphoma, there is a correlation between freedom from recurrence and persistent PCR negativity for bcl-2 rearrangement-containing cells in follow-up bone marrow samples.
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PMID:High-dose treatment with autologous haemopoietic progenitor cell support for large B-cell, follicular and mantle-cell lymphoma. 1246


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