Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to investigate the prognostic effects of four biological markers, BCL2, TP53, Ki-67, and P-glycoprotein, and their possible clinical relevance in addition to the international prognostic index (IPI) in diffuse large B-cell lymphoma (DLBCL). A total of 405 patients with aggressive lymphoma, stage II-IV, between 18 and 67 years, were randomized in a trial comparing CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) with MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin). Of these, 267 cases were classified as DLBCL, with adequate paraffin blocks available in 207 cases, enabling immunohistochemical assessment of the expression of BCL2, TP53, P-glycoprotein, and Ki-67. In a multivariate analysis, stratified for IPI, high BCL2 expression (>10%) low (<60%) expression of Ki-67, and high TP53 protein expression (>75%) were shown to provide additional prognostic information with regard to overall or failure-free survival. We found no association between expression of P-glycoprotein and outcome. Assessment of BCL2 positivity might be introduced as part of the routine investigation in patients with DLBCL, but further studies are necessary to confirm the clinical relevance of Ki-67 and TP53 expression.
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PMID:Assessment of biological prognostic factors provides clinically relevant information in patients with diffuse large B-cell lymphoma--a Nordic Lymphoma Group study. 1508 85

We report a case of composite lymphoma consisting of peripheral T-cell lymphoma and an anaplastic variant of diffuse large B-cell lymphoma (DLBCL) and associated with Epstein-Barr virus (EBV) infection and strong p53 expression. A 65-year-old Japanese woman developed fever and generalized lymphadenopathy. A biopsy of the cervical node revealed the morphology of malignant lymphoma with 2 kinds of lymphoma coexisting in 1 lymph node. One lymphoma type consisted of immunoblastic large cells with the T-cell marker phenotype CD3+, CD45RO/UCHL-1+, CD20/L26-, CD79-, CD10-, CD30-, and CD15-; the other type consisted of large cells with abundant cytoplasm and pleomorphic nuclei with the marker phenotype CD79+, CD20/L26+, CD45RO/UCHL-1-, CD3-, CD10-, CD30+, NPM/ALK-, and CD15-. Therefore, the diagnosis was composite lymphoma of peripheral T-cell lymphoma and an anaplastic variant of DLBCL, stage IVB, because the patient had bone marrow involvement with peripheral T-cell lymphoma. The biopsy led to findings of latent type II EBV-associated lymphoma in both the peripheral T-cell lymphoma and the anaplastic variant of DLBCL as the result of positive signals for EBV small RNAs by in situ hybridization, positive immunostaining results for EBV latent membrane protein 1 antibody, and negative immunostaining results for EBV nuclear antigen 2. Immunostaining of the mass with p53 antibody also yielded positive results for both types of lymphoma cells. This case suggests that the immunocompromised state of this patient with EBV-related peripheral T-cell lymphoma allowed the emergence of an EBV-related anaplastic variant of DLBCL and suggests a close relationship between p53 expression and latent EBV infection.
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PMID:Epstein-Barr virus-associated composite lymphoma composed of peripheral T-cell lymphoma and an anaplastic variant of a diffuse large B-cell type of non-Hodgkin's lymphoma and strongly expressing p53 protein. 1516 95

Controversy still exists over the response to therapy and prognosis of patients with primary mediastinal B-cell lymphoma (PMBL). Recent data from the International Extranodal Lymphoma Study Group (IELSG) suggest that a MACOP-B (methotrexate, adriamycin, cyclophosphamide, vincristine, prednisone, bleomycin) chemotherapy regimen followed by radiotherapy may be a better induction strategy than other previously used treatments. Although the pathobiology of PMBL has been widely studied, its precise histology, phenotype, and molecular characteristics are still not clear. To date, phenotypic analysis has revealed the following phenotype: positivity for CD45 and CD20, but negativity for CD3, CD10, CD21, Class I/II major histocompatibility antigens, and a variety of other immunohistochemical markers. CD79a is generally detected, despite an absence of surface immunoglobulins (Igs). CD30 staining is observed in most cases, but is weaker and less homogeneous than in classic Hodgkin's lymphoma or anaplastic large cell lymphoma. BCL-2 protein is usually expressed but there are few data describing the expression of MUM1/IRF4, PAX5/BSAP, BCL-6, or the B-cell transcription factors BOB.1, Oct-2, and PU.1. Cytogenetic studies reveal gains in segments of chromosome 9p, including amplification of the REL proto-oncogene and the tyrosine kinase gene JAK2. Other molecular findings include: C-myc mutations or rearrangements, p53 mutations, IgV(H), gene mutations, and bcl-2 and mal over-expression. bcl-6 mutations and bcl-2 gene rearrangements are generally absent, suggesting that PMBL is of pre-germinal center (GC) origin. However, two recent reports show isotype-switched Ig genes with a high frequency of somatic hypermutations as well as variants in the 5' noncoding region of the bcl-6 gene. The IELSG collected 137 PMBL cases for extensive pathologic review. Histologically, the lymphomatous growth was predominantly diffuse with sclerosis that induced compartmentalized cell aggregation. It consisted of large cells with varying degrees of nuclear polymorphism and clear to basophilic cytoplasm. Molecular analysis was performed on 40 cases and showed novel findings. More than half of the cases displayed bcl-6 gene mutations, which usually occurred together with functioning somatic IgV(H) gene mutations, and BCL-6 and/or MUM1/IRF4 expression. The present study supports the concept that PBML is derived from activated GC or post-germinal center cells. However, it differs from other aggressive B-cell lymphomas in that it shows defective Ig production despite the expression of Oct-2, BOB.1, and PU.1 transcription factors, and a lack of IgV(H) gene crippling mutations.
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PMID:Pathobiology of primary mediastinal B-cell lymphoma. 1520 21

Progression of follicular lymphomas (FLs) is often accompanied by a spectrum of histologic changes and an aggressive clinical course. Although molecular alterations have been implicated in this event, the underlying factors are largely unknown. We studied the expression of selected tumor suppressor genes (P53 and retinoblastoma [RB]), oncogenes (MYC and BCL2), and a transferrin-receptor related protein (Trump) in sequential biopsies in 16 patients. Eleven patients progressed from grade I or II FL to aggressive B-cell lymphomas with diffuse morphology, whereas 5 patients presented with diffuse aggressive lymphomas and recurred with indolent lymphomas. Immunoreactivity for P53 correlated with higher histologic grade in lymphomas progressing from indolent to aggressive; however, only 1 patient who presented with aggressive lymphoma demonstrated a P53 gene mutation. Neither P53 immunoreactivity nor genotypic alterations correlated with presentation with an aggressive histology and relapse with FL. Growth fraction, as assessed by Ki-67 staining, and Trump expression correlated with histologic grade. Immunoreactivity for RB, BCL2, and MYC was seldom associated with progression. Eight of 9 cases tested exhibited identical immunoglobulin heavy and light chain rearrangements or identical BCL2 gene rearrangements in the sequential lymphomas. We conclude that P53 and Trump protein expression and proliferation activity correlate with histologic grade, but not with recurrence or progression of FL. Our results further indicate that progression of FL to diffuse aggressive lymphomas and presentation of an aggressive B-cell lymphoma followed by FL are clonally related.
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PMID:Immunophenotypic and genotypic characterization of progression in follicular lymphomas. 1535 33

Rituximab is widely used for the treatment of B-cell non-Hodgkin's lymphoma (NHL), and encouraging results have been obtained. However, some CD20-positive NHL show minimal response to rituximab, indicating that the treatment effect depends on the presence or absence of an unidentified factor. We analyzed the relationship between the effect of rituximab plus chemotherapy and expression of Ki-67, p53 and bcl-2 and several clinical variables in cases of B-NHL, particularly follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Forty-four patients were included in the present study, and the overall treatment response rate was 68%. Twelve of 30 patients (40%) achieved a complete response, five (16%) reached an unconfirmed complete response and 13 (43%) achieved a partial response. A high serum lactate dehydrogenase level and International Prognostic Index of high or high intermediate risk were associated with a decreased response in the case of FL. Immunohistochemical assays were performed in 18 FL patients (55%) and 15 DLBCL patients (45%). Significant correlation was found between an inferior response to treatment and high Ki-67 expression in the cases of FL (P = 0.006). p53 and bcl-2 expression did not correlate significantly with the response rate. The cell cycle appears to be an important factor in the efficacy of rituximab treatment. Ki-67 expression might be a predictor of efficacy of rituximab plus chemotherapy.
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PMID:Efficacy of rituximab plus chemotherapy in follicular lymphoma depends on Ki-67 expression. 1536 34

The human proto-oncogene BCL6 encodes a BTB/POZ-zinc-finger transcriptional repressor that is necessary for germinal-centre formation and is implicated in the pathogenesis of B-cell lymphoma. The precise function of BCL6 in germinal-centre development and lymphomagenesis is unclear because very few direct BCL6 target genes have been identified. Here we report that BCL6 suppresses the expression of the p53 (also known as tp53) tumour suppressor gene and modulates DNA damage-induced apoptotic responses in germinal-centre B cells. BCL6 represses p53 transcription by binding two specific DNA sites within the p53 promoter region and, accordingly, p53 expression is absent in germinal-centre B cells where BCL6 is highly expressed. Suppression of BCL6 expression via specific short interfering RNA leads to increased levels of p53 messenger RNA and protein both under basal conditions and in response to DNA damage. Most notably, constitutive expression of BCL6 protects B cell lines from apoptosis induced by DNA damage. These results suggest that an important function of BCL6 is to allow germinal-centre B cells to tolerate the physiological DNA breaks required for immunoglobulin class switch recombination and somatic hypermutation without inducing a p53-dependent apoptotic response. These findings also imply that deregulated BCL6 expression contributes to lymphomagenesis in part by functional inactivation of p53.
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PMID:The BCL6 proto-oncogene suppresses p53 expression in germinal-centre B cells. 1557 13

Plasmablastic lymphoma is an aggressive neoplasm that shares many cytomorphologic and immunophenotypic features with plasmablastic plasma cell myeloma. However, plasmablastic lymphoma is listed in the World Health Organization (WHO) classification as a variant of diffuse large B-cell lymphoma. To characterize the relationship between plasmablastic lymphoma and plasmablastic plasma cell myeloma, we performed immunohistochemistry using a large panel of B-cell and plasma cell markers on nine cases of plasmablastic lymphoma and seven cases of plasmablastic plasma cell myeloma with and without HIV/AIDS. The expression profiles of the tumor suppressor genes p53, p16, and p27, and the presence of Epstein-Barr virus (EBV) and human herpes virus type 8 (HHV-8) were also analyzed. All cases of plasmablastic lymphoma and plasmablastic plasma cell myeloma were positive for MUM1/IRF4, CD138, and CD38, and negative for CD20, corresponding to a plasma cell immunophenotype. PAX-5 and BCL-6 were weakly positive in 2/9 and 1/5 plasmablastic lymphomas, and negative in all plasmablastic plasma cell myelomas. Three markers that are often aberrantly expressed in cases of plasma cell myelomas, CD56, CD4 and CD10, were positive in 5/9, 2/5, and 6/9 plasmablastic lymphomas, and in 3/7, 1/5, and 2/7 plasmablastic plasma cell myelomas. A high Ki-67 proliferation index, overexpression of p53, and loss of expression of p16 and p27 were present in both tumors. No evidence of HHV-8 infection was detected in either neoplasm. The only significant difference between plasmablastic lymphoma and plasma cell myeloma was the presence of EBV-encoded RNA, which was positive in all plasmablastic lymphoma cases tested and negative in all plasma cell myelomas. In conclusion, most cases of AIDS-related plasmablastic lymphoma have an immunophenotype and tumor suppressor gene expression profile virtually identical to plasmablastic plasma cell myeloma, and unlike diffuse large B-cell lymphoma. These results do not support the suggestion in the WHO classification that plasmablastic lymphoma is a variant of diffuse large B-cell lymphoma.
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PMID:Plasmablastic lymphomas and plasmablastic plasma cell myelomas have nearly identical immunophenotypic profiles. 1557 69

We report a case of a simultaneous occurrence of medullary and papillary carcinomas of the thyroid gland with metastases of a papillary carcinoma to the cervical lymph nodes and a concurrent small B-cell lymphocytic lymphoma revealed in the lymph nodes examined in a 71-year-old woman. The diagnosis was based on microscopic examination of surgical specimens and supported by immunohistochemistry. Additionally, P53 and RET mutation analysis was performed. In this case, the coincidence of medullary and papillary carcinomas of the thyroid gland may account for a true composite tumor. The coexistence of a small B-cell lymphoma in our patient may be explained by irradiation treatment undergone during the adolescence.
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PMID:Simultaneous occurrence of medullary and papillary carcinomas of the thyroid gland with metastases of papillary carcinoma to the cervical lymph nodes and the coinciding small B-cell lymphocytic lymphoma of the lymph nodes--a case report. 1561 77

The BCL-2 family has been implicated in the pathogenesis of various hematopoietic malignancies, including follicular non-Hodgkin lymphoma and B-cell chronic lymphocytic leukemia. To identify genes that act synergistically in BCL2-enforced leukemogenesis, we developed a murine B-cell lymphoma/leukemia model based on the IL-3-dependent Balb/C pro-B line (FL5.12). FL5.12 cells were stably transfected with antiapoptotic BCL-2 alone or in combination with proapoptotic BAX or nonfunctional mutant BAX, thereby creating various levels of imbalance within the BCL-2 family. Transfectants were intravenously injected into normal Balb/C mice. Whereas FL5.12 cells did not provoke leukemia, mice injected with stable transfectants died of leukemia over time. Disease incidence and latency time depended on the degree of imbalance in the BCL-2 family, supporting a model whereby BCL2 drives tumorigenesis. All mice presented with hepatosplenomegaly and leukemic FL5.12 cells in peripheral blood and bone marrow compartments. Leukemic conversion was accompanied by secondary genetic aberrations leading to clonal IL-3-responsive leukemia. Cellular transformation was independent of alterations in c-Myc or downstream apoptotic pathway. Leukemic clones retained a normal DNA damage response leading to elevated P53 and P21 levels and cell cycle arrest upon irradiation. In conclusion, our mouse model may prove a valuable tool to identify genes that cooperate in BCL2-enforced lymphoma/leukemogenesis.
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PMID:Novel murine B-cell lymphoma/leukemia model to study BCL2-driven oncogenesis. 1564 25

To study the apoptosis and its mechanism at the fetal-maternal interface of early gestation, localization of apoptotic cells in the implantation sites of the rhesus monkey on day 17, 19, 28 and 34 of pregnancy were first examine by using the TUNEL technique. The expression of Ki67, a molecular marker of proliferating cells, and two apoptotic proteins, B cell lymphoma/leukaemia-2 (Bcl-2) and P53, were then studied by immunohistochemistry. Apoptotic nuclei were observed mainly in the syncytiotrophoblast. Ki67 was confined almost exclusively to cytotrophoblasts. The localization of Bcl-2 protein follows that of the apoptotic nuclei and its expression level increased as the development of the placenta progressed on. P53 was detected to some extent in cytotrophoblasts and syncytiotrophoblast covering the basal feet of the anchoring villi during the late stage of placentation. Based on these observations, it might be suggested that Bcl-2 could be possible to play an interesting role in limiting degree of nuclear degradation and sustaining cell survival in the multi-nucleated syncytiotrophoblast cells during early pregnancy, and P53 could also be essential in regulating the trophoblastic homeostasis by controlling its proliferation or apoptosis.
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PMID:Expression of Bcl-2 and p53 at the fetal-maternal interface of rhesus monkey. 1564 34


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