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Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies have shown bcl-2 to be regulated by p53. Other studies have suggested an inverse relationship between p53 and bcl-2 protein expression in breast and colonic cancers and in a variety of subtypes of non-Hodgkin's lymphoma. This study investigates the relationship between bcl-2 and p53 protein expression and the correlation between these findings and the grade and cell type of follicular lymphomas according to the REAL classification. Paraffin-embedded nodal follicular lymphomas (n = 37) were subjected to bcl-2 and p53 immunohistochemistry on tissue sections using a three-step ABC system. Positive immunostaining for both oncoproteins was scored using a three-tiered scale: +, < 10 per cent cells; ++, 10-50 per cent cells; and ++(+), > 50 per cent cells (< 10 per cent was used as a cut-off to define negative tumours). Ninety-seven per cent (36/37) of follicular lymphomas expressed bcl-2 protein in all three grades, manifesting in the small cell (grade 1) through to the large cell (grade 3). p53 protein expression showed a pattern of increasing immunostaining with progression towards the high-grade follicular lymphoma: grade 1 = 6 per cent (1/16); grade 2 = 48 per cent (10/21); grade 3 = 100 per cent (6/6). Five cases comprised varying combinations of grades. This latter finding suggests a role for p53 mutation in the progression/transformation of follicular lymphoma. The mechanism, however, differs from that suggested in breast and colonic cancers, since an inverse relationship between bcl-2 and p53 was not demonstrated in the present study.
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PMID:bcl-2 and p53 protein expression in follicular lymphoma. 934 33

We have identified three unbalanced translocations involving chromosomes 5 and 17, der(5)t(5;17), der(17)t(5;17), and dic(5;17), in the malignant cells from 17 patients with myeloid neoplasms. Six patients had a primary myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) de novo; ten patients had therapy-related MDS and/or AML (t-MDS/t-AML), and one patient had chronic myelogenous leukemia in myeloid blast phase. Two of the six patients with MDS or AML de novo had extensive exposure to industrial solvents, and one patient had Seckel syndrome. The primary diagnoses for the ten patients with t-MDS/t-AML were breast carcinoma and Hodgkin's disease in two patients each, and non-Hodgkin's lymphoma, multiple myeloma, chronic lymphocytic leukemia, ovarian carcinoma, thyroid carcinoma, and rhabdomyosarcoma in one patient each. Four patients had received both prior chemotherapy and radiotherapy, four others received prior chemotherapy only, and the remaining two patients only prior radiotherapy. Fluorescence in situ hybridization of centromere-specific probes for chromosomes 5 and 17 revealed that a dicentric rearrangement was the most common (13/16 patients examined). The genetic consequences of these chromosomal rearrangements are partial monosomy for 5q and 17p. Two of six patients examined had point mutations in TP53, suggesting that loss of function of TP53 in addition to loss of a tumor suppressor gene on 5q may be involved in the pathogenesis of the malignant disease in some of these patients.
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PMID:dic(5;17): a recurring abnormality in malignant myeloid disorders associated with mutations of TP53. 936 36

We have recently reported a series of 15 non-villous splenic marginal zone lymphoma patients, six of whom showed p53 mutations (40%). This molecular alteration did not correlate with any particular clinico-pathologic feature at diagnosis. After a median follow-up of 56 months, four cases evolved into aggressive fatal non-Hodgkin's lymphoma (NHL) and two had refractory progressive disease; interestingly, p53 mutations were demonstrated in five of these patients at diagnosis. As the patients with wild-type p53 presented responsive or indolent disease, this genetic alteration may be an early marker of aggressive transformation or refractoriness. p53 evaluation at diagnosis could be advisable in this particular subset of NHL.
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PMID:Poor prognosis in non-villous splenic marginal zone cell lymphoma is associated with p53 mutations. 937 58

Myelodysplastic syndrome (MDS) is an uncommon but serious complication of patients who undergo autologous bone marrow transplantation (auto-BMT) for non-Hodgkin's lymphoma or Hodgkin's disease. Some patients exhibit an indolent course, but others succumb to aggressive disease. p53 overexpression is rare in de novo MDS but common in therapy-associated MDS. We used an immunostaining method to analyze expression of p53, the p53-associated tumor suppressor gene products, MDM2, p21waf1, retinoblastoma gene protein (pRB), and the antiapoptotic oncoprotein bcl-2 before and after BMT in BM specimens from eight patients with clonal karyotypic abnormalities characteristic of MDS. Staining was compared with findings in normal BM specimens and specimens from auto-BMT controls and patients with de novo MDS. p53 protein was found in three (75%) of four post-transplantation specimens from patients in whom a clinically aggressive form of MDS developed. In contrast, p53 was absent in all of the specimens from four patients with karyotypic evidence of MDS, but with indolent disease. bcl-2 protein was overexpressed by immature myeloid cells in seven of eight pre-BMT specimens. After BMT, it was predominantly found at low levels in cases positive for p53. MDM2 was present only after transplantation and was found with equal frequency in patients with indolent and aggressive MDS. We detected p21waf1 in only one aggressive post-BMT MDS specimen. pRB was normally expressed in all of the specimens. These data show that p53 and bcl-2 staining patterns in post-transplantation MDS are similar to those described in therapy-associated MDS. p53 positivity is associated with poor prognosis in auto-BMT patients with MDS. Expression of MDM2, p21waf1, and pRB in this group of patients is not helpful in predicting outcome.
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PMID:Expression of p53, MDM2, p21waf1, bcl-2, and retinoblastoma gene proteins in myelodysplastic syndrome after autologous bone marrow transplantation for lymphoma. 938 63

In several types of solid tumours, circulating antibodies to p53 are seen in about a third of cases with a p53 mutation, but are absent in cases without p53 mutation. Therefore detection of those antibodies has relatively low sensitivity but high specificity in the detection of p53 mutations. We looked for circulating p53 antibodies by ELISA in 56 adult non-Hodgkin's lymphoma (NHL) and 80 multiple myeloma cases. A certain or highly probable p53 mutation was found by SSCP analysis, immunocyto- or immunohistochemistry in 8/35 (23%) NHL cases and 2/19 (10%) MM cases analysed by these techniques. None of the 80 MM cases and only one of the 56 cases of NHL had circulating p53 antibodies. The positive case had Burkitt's lymphoma and a p53 missense mutation at codon 273. Thus, very few MM and NHL patients with a p53 mutation develop p53 antibodies and this test does not appear to be useful in haematological malignancies.
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PMID:Very low incidence of p53 antibodies in adult non-Hodgkin's lymphoma and multiple myeloma. 945 Aug 8

A high incidence of non-Hodgkin's lymphoma of the pleural cavity has developed in Japanese patients with long-standing pyothorax (38 years on average) resulting from artificial pneumothorax for the treatment of pulmonary tuberculosis or tuberculous pleuritis. Patients with pyothorax-associated lymphoma (PAL) have long been exposed to antituberculous drugs, antibiotics, bacterial or viral products, and frequent diagnostic radiation for the confirmation of pneumothorax and pyothorax. We analyzed p53 mutations on paraffin-embedded specimens from 21 patients with PAL by PCR-single-strand conformational polymorphism followed by direct sequencing. An unusually high frequency of p53 mutations (14 of 21 cases, 67%) was detected in the PAL specimens, and mutations consisted of 13 nucleotide substitutions and 1 deletion. Furthermore, 10 of 13 substitutions (77%) occurred at dipyrimidine sites (CC:GG to CT:GA substitution). Such specificity has not been reported, except for solar light-related skin cancer and AIDS-related lymphoma in some parts. An UV light mimetic agent may be produced in the long history of chronic inflammation in tuberculosis or immunodeficient patients.
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PMID:Frequent p53 mutations at dipyrimidine sites in patients with pyothorax-associated lymphoma. 951 88

Hepatitis C virus (HCV) infection may be complicated by non-Hodgkin's lymphoma. We describe eight cases of B-cell extranodal non-Hodgkin's lymphoma occurring during the course of chronic HCV-related hepatic disease (low-grade of mucosa-associated lymphoid tissue [MALT]-type; diffuse large cell; Burkitt; diffuse small cell). Some were localized to the liver (2), liver and spleen (1), spleen (1), peritoneal cavity (1), parotid gland (1); others manifested in the nasopharynx (1) and eyelid (1) but were accompanied by nodal disease. Four lymphomatous specimens available for molecular analysis exhibited clonal immunoglobulin gene rearrangements, lacked bcl-2, bcl-6, c-myc genes and p53 alterations, and did not contain replicative intermediate HCV RNA, as documented by a strand-specific reverse transcriptase-polymerase chain reaction. Low levels of positive-strand HCV RNA were detected in a single hepatic lymphoma, suggesting the presence of the virus in residual hepatocytes. The antigen-driven properties of HCV-associated B-cell malignant neoplasms may be considered for hepatic MALT-type lymphoma, which probably originated from lymphoid tissue acquired during long-standing HCV infection.
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PMID:Extranodal lymphomas associated with hepatitis C virus infection. 957 65

Accumulation of the p53 protein has been found in several types of lymphomas. However, p53 gene mutations have been infrequently demonstrated in some specific types of lymphomas. In the present study, a correlation between p53 immunoreactivity and p53 gene mutations in a large panel of non-Hodgkin's lymphoma (NHL) cases is attempted. A panel of 202 cases of NHL was evaluated by immunohistochemical staining for p53 protein. All cases that were immunohistochemically positive for p53 protein were analyzed by the polymerase chain reaction (PCR) single strand conformation polymorphism (SSCP) method to identify mutations within the p53 gene. In order to confirm the mutation, sequencing of PCR-amplified p53 gene segments was performed. Overexpression of p53 protein was found in 59 of the 202 cases of NHL, but only four of these 59 cases showed a shift on SSCP analysis, and point mutations were detected in three of them by the subsequent sequencing. p53 immunoreactivity was generally greater in high-grade lymphoma. The results of this study suggest that immunohistochemical reactivity for p53 protein is not a reliable indicator of the presence of their structural alterations of p53 gene exons 4-9 in NHL.
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PMID:p53 protein expression in non-Hodgkin's lymphomas is infrequently related to p53 gene mutations. 958 59

The expression of p53 and PCNA on deparaffinized sections of tumor was assessed in relation to the International Index and response to chemotherapy. Thirty-five non-Hodgkin's lymphoma (NHL) patients were divided into three groups: aggressive NHL, mantle cell lymphoma (MCL), and low-grade NHL. None of the expressions correlated with the International Index or early response to chemotherapy in any group. In low-grade NHL, none of the patients expressed p53. Only one of three patients with overexpression of p53 showed conformational change and alteration of sequence in exon 7 by PCR-SSCP and DNA sequencing. The results showed that p53 and PCNA staining were not useful for predicting early response to chemotherapy, and that their expressions had no correlation with the International Index.
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PMID:Expressions of p53 and PCNA do not correlate with the international index or early response to chemotherapy in non-Hodgkin's lymphoma. 959 Jan 48

In this study, we investigated the extent of apoptosis in 82 non-Hodgkin's lymphoma and 4 reactive follicular hyperplasias and correlated the findings with the extent of apoptosis as determined by the 3'-end labelling method of the apoptotic DNA. To study the influence of apoptosis-regulating proteins bcl-2, bax, mcl-1 and p53 on the extent of apoptosis, we also immunostained the samples with antibodies to them. The results show that there is a significant difference in the extent of apoptosis between low- and high-grade non-Hodgkin's lymphomas, the latter on average showing considerably more apoptotic cells (0.38 +/- 0.30 and 1.44 +/- 1.35%, respectively; p = 0.001). In line with this difference, high-grade lymphomas had significantly more cases with a weak expression of bcl-2 and strong expression of bax (p = 0.00008 and p = 0.016, respectively). They also showed significantly more cases with a positive p53 immunoreactivity (p < 0.00001) and strong mcl-1 immunoreactivity (p = 0.018). The results suggest that apoptosis-affecting genes bcl-2, bax, mcl-1 and p53 all take part in the regulation of apoptosis in malignant non-Hodgkin's lymphomas and contribute to a different level of apoptosis between high- and low-grade non-Hodgkin's lymphomas.
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PMID:High-grade malignant non-Hodgkin's lymphomas differ from low-grade lymphomas in the extent of apoptosis and their expression of bcl-2, mcl-1, bax and p53. 959 Oct 44


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