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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bcl2 is an important protein involved in the pathogenesis of follicular lymphoma (FL). However, approximately 10% of FL cases do not express Bcl2. The present study was designed to compare gene aberrations, prosurvival gene expression, apoptosis and proliferation rates in Bcl2-positive and -negative FL cases. Bcl2 translocation and Bcl6 translocation were detected and compared using fluorescence in situ hybridization (FISH). A tendency for Bcl6 translocation to occur was found more frequently in Bcl2-negative FL than in the Bcl2-positive cases. The expression of Bcl-X, BAX, p53, Bcl6 was analyzed by immunohistochemistry. Bcl2 family proteins Bcl-X and BAX were expressed similarly in the two FL types. In some cases of Bcl2-negative FL there was high expression of Bcl6 or p53 but no such Bcl2-positive FL cases were detected. Furthermore, there was an inverse relationship between the expression of Bcl6 and p53. These results indicate that the Bcl6 translocation occurs more frequently in Bcl2-negative FL. Furthermore, other prosurvival proteins such as p53 and Bcl6 may play an important role in the pathogenesis of Bcl2-negative FL.
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PMID:Bcl2-negative follicular lymphomas frequently have Bcl6 translocation and/or Bcl6 or p53 expression. 1729 47

Chromobox 7 (CBX7) is a chromobox family protein and a component of the Polycomb repressive complex 1 (PRC1) that extends the lifespan of cultured epithelial cells and can act independently of BMI-1 to repress the INK4a/ARF tumor suppressor locus. To determine whether CBX7 might be oncogenic, we examined its expression pattern in a range of normal human tissues and tumor samples. CBX7 was expressed at high levels in germinal center lymphocytes and germinal center-derived follicular lymphomas, where elevated expression correlated with high c-Myc expression and a more advanced tumor grade. By targeting Cbx7 expression to the lymphoid compartment in mice, we showed that Cbx7 can initiate T cell lymphomagenesis and cooperate with c-Myc to produce highly aggressive B cell lymphomas. Furthermore, Cbx7 repressed transcription from the Ink4a/Arf locus and acted epistatically to the Arf-p53 pathway during tumorigenesis. These data identify CBX7 as a chromobox protein causally linked to cancer development and may help explain the low frequency of INK4a/ARF mutations observed in human follicular lymphoma.
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PMID:Role of the chromobox protein CBX7 in lymphomagenesis. 1737 22

Very low-dose irradiation (2 x 2 Gy) is a new, effective, and safe local treatment for follicular lymphoma. To understand the biologic mechanisms of this extremely effective response, we compared by microarray the gene-expression profile of patients' biopsies taken before and after radiation. In all patients, a major and consistent induction of p53 target genes was seen. p53 targets involved in cell-cycle arrest and apoptosis showed the same mode of regulation, indicating that, in vivo, both are activated simultaneously. p53 up-regulation and p53-mediated proliferation arrest and apoptosis were substantiated using immunohistochemistry, with activation of both the intrinsic and the extrinsic apoptotic pathways. The other induced genes revealed a whole set of biologically meaningful genes related to macrophage activation and TH1 immune response. Immunohistochemical analysis suggested a specific activation or differentiation of resident macrophages by apoptotic cells. These biologic insights are important arguments to advocate the use of low-dose radiotherapy as an effective palliative treatment for follicular lymphoma. Moreover, this study is the first in vivo report of the radiation-induced p53 apoptotic response in patients and suggests that this apoptotic response is not immunologically silent.
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PMID:In vivo p53 response and immune reaction underlie highly effective low-dose radiotherapy in follicular lymphoma. 1748 95

Single-nucleotide polymorphism (SNP) array analysis was performed using the 10K GeneChip array on a series of 26 paired follicular lymphoma (FL) and transformed-FL (t-FL) biopsies and the lymphoma cell lines SCI-1, DoHH2 and RL2261. Regions of acquired homozygosity were detected in 43/52 (83%) primary specimens with a mean of 1.7 and 3.0 aberrations in the FL and t-FL, respectively. A notable feature was the occurrence of recurring sites of acquired uniparental disomy (aUDP) on 6p, 9p, 12q and 17p in cell lines and primary samples. Homozygosity of 9p and 17p arose predominantly in t-FL and in three cases rendered the cell homozygous for a pre-existing mutation of either CDKN2A or TP53. These data suggest that mutation precedes mitotic recombination, which leads to the removal of the remaining wild-type allele. In all, 18 cases exhibited abnormalities in both FL and t-FL samples. In 10 cases blocks of homozygosity were detected in FL that were absent in the subsequent t-FL sample. These differences support the notion that FL and t-FL may arise in a proportion of patients by divergence from a common malignant ancestor cell rather than by clonal evolution from an antecedent FL.
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PMID:Genome-wide detection of recurring sites of uniparental disomy in follicular and transformed follicular lymphoma. 1749 76

To clarify whether p53 mutation could be involved in the pathogenesis of various subtypes of lymphoma, we investigated 62 Japanese cases of non-Hodgkin's lymphomas (NHLs) for p53 gene mutations and their relationship with the expression of p53 protein. Mutations in exons 5-9 of the p53 gene were screened for using the non-isotopic RNase cleavage assay (NIRCA) and confirmed by direct sequencing, followed by immunohistochemical analysis for p53 protein. Missense and/or nonsense mutations of p53 were detected in 3 (10.7%) of 28 diffuse large B-cell lymphomas (DLBLs) and 2 (15.4%) of 13 T-cell NHLs (15.4%). A single missense mutation at codon 157 (Val to Phe) in exon 5 and at codon 273 (Arg to Pro) in exon 8 was found respectively in 2 DLBLs and in one peripheral T-cell lymphoma (unspecified). In these 3 cases harbouring a missense mutation, overexpression of p53 protein was observed in more than 80% of tumour cells. Double transversion mutations comprising of a missense mutation at codon 167 (Gln to His) in exon 5 and a nonsense mutation at codon 183 (Ser to stop codon) in exon 5 were detected in one DLBL that had apparently transformed from follicular lymphoma and in one advanced adult T-cell lymphoma (ATL). In these two cases harbouring p53 nonsense mutation, no cells positive for p53 protein immunostaining were detected, as well as lymphomas without p53 mutation.
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PMID:Mutation of the p53 tumour suppressor gene and overexpression of its protein in 62 Japanese non-Hodgkin's lymphomas. 1760 75

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

We used a standardized electrophoresis protocol to identify differentially expressed proteins based on a sample pooling approach comparing three follicular lymphoma and three mantle cell lymphoma-derived cell lines. One hundred and seventy-five consistently differentially expressed proteins were identified out of more than 1600 protein spots per gel. Of these 175 protein spots, 38 of the 41 most highly expressed proteins were identified by MS analysis (MALDI-TOF), involving different cellular programs such as DNA repair (Rad50), cell cycle control (Mad1L1), transcription (SAFB), and apoptosis (Luca-15 protein). Expression data were confirmed by Western blot analysis of identified proteins and 2-D gel hybridization of proteins with known overexpression (G1/S-specific cyclin-D1, apoptosis regulator Bcl-2). Comparison of proteome analysis to RNA expression array data revealed only a modest correlation of RNA and protein level emphasizing the relevance of post-translational regulation in lymphomagenesis (p = 0.36). Most interestingly, additional data bank search identified 13 out of 17 referenced proteins (76%) as members of a TP53-dependent network of cell regulation.
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PMID:Proteome- and microarray-based expression analysis of lymphoma cell lines identifies a p53-centered cluster of differentially expressed proteins in mantle cell and follicular lymphoma. 1799 Feb 59

Low dose radiotherapy is an effective palliative treatment for follicular lymphoma, inducing the rapid apoptosis of the neoplastic B cells. Comparison of the gene expression profiles of follicular lymphoma biopsy samples taken before and after radiation shows that the intact p53 pathway is the driving force to the apoptotic process. Death of the Bcl-2 overexpressing B cells can be explained by the prominent induction of the extrinsic apoptotic pathway, with an active role of the neoplastic microenvironment for the expression of death receptor ligands and the clearance of the apoptotic cells. These insights have implications for the design of new protocols in the treatment of follicular lymphoma.
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PMID:The role of the p53 pathway in the treatment of follicular lymphoma. 1823 30

The International Prognostic Index and the Follicular Lymphoma International Prognostic Index are widely used for the risk assessment of follicular lymphoma (FL). Although molecular studies have provided insight into the biology of FL, no molecular marker has impacted on treatment stratification. Because TP53 mutations are associated with poor prognosis in hematologic malignancies, we investigated the prognostic value of TP53 mutation at diagnosis in FL. Heterozygous TP53 mutation was detected in 12 of 185 (6%) analyzed cases. Mutation was associated with older age (P = .02) and higher International Prognostic Index score (P = .04). On multivariate analysis, TP53 mutation correlated with shorter progression-free survival (P < .001) and overall survival (P = .009). TP53 mutation was associated with low expression of the immune-response 1 gene expression signature (P = .016) and with an unfavorable gene expression-based survival predictor score (P < .001), demonstrating for the first time that molecular features of the malignant cell may correlate with the nature of the immune response in FL.
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PMID:The presence of TP53 mutation at diagnosis of follicular lymphoma identifies a high-risk group of patients with shortened time to disease progression and poorer overall survival. 1884 Jul 14

This study investigated the prevalence of Epstein-Barr virus (EBV) infection and its association with P53 expression in a panel of 87 previously untreated nodal non-Hodgkin lymphomas (NHLs) from India. Polymerase chain reaction specific for Epstein Barr nuclear antigen 1 (EBNA1) and EBNA-3C was performed on the lymphnode tissue DNA, while P53 expression was analyzed by immunohistochemistry. EBV, predominantly type A strain, was detected in 27/87 (31%) nodal lymphoid malignancies, 11/46 diffuse large B-cell lymphomas, 6/17 follicular lymphoma, 4/6 anaplastic large cell lymphomas (ALCL), 5/11 peripheral T-cell lymphomas (PTCL) and 1/7 lymphoblastic lymphomas. EBV infection was more frequently observed in a specific subset of nodal NHL, suggesting a causative role of EBV infection in the pathogenesis of ALCL and PTCL. There was no significant association between EBV and P53 expression in our series of NHL patients.
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PMID:Frequency and distribution of Epstein-Barr virus infection and its association with P53 expression in a series of primary nodal non-Hodgkin lymphoma patients from South India. 1905 47


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