Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The roles of the bcl-2 and p53 proteins in Hodgkin's disease (HD) are poorly understood. We therefore compared their detected presence in Hodgkin and Reed-Sternberg/large atypical (H-RS/LA) cells immunohistochemically with the percentages of these cells double-labeled for CD30 and DNA strand breaks (DNA fragmentation index, DFI); mitotic indices (MI); and the EBV infection status. We found a highly significant inverse correlation between the fractions per case of H-RS/LA cells expressing bcl-2/p53 proteins and the DFI of CD30+ elements. No marked effect of these two oncoproteins on MI was noticed, although these parameters and DFI of CD30+ cells were linearly related. EBV infection of H-RS/LA cells exerted only a limited effect on the parameters tested. The results of this study suggest that overexpressed bcl-2 and, to some extent, p53 proteins in H-RS/LA cells of HD primarily counteract deletion of these cells.
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PMID:Mitotic activity and nuclear DNA damage of large cells in Hodgkin's disease: comparison with the expression of p53 and bcl-2 proteins and the presence of Epstein-Barr virus. 913 Jun 23

A discordance between p53 protein overexpression and the presence of mutations in the gene has been observed in many types of tumors, including human lymphomas. To probe this finding, we have studied a large series of 94 lymphomas of different pathologic types and histologic differentiation. Analyzing exons 5-9, we have found mutations in the p53 gene in 7 of 94 cases distributed in different subtypes: 4/12 (33%) high-grade B-cell non-Hodgkin's lymphomas (B-NHLs), in 1 of 5 (20%) high-grade mucosa-associated lymphomas (MALT), in 1 of 22 (4.5%) anaplastic large cell lymphoma (ALCL), and in 1 of 24 (4%) T-cell NHLs. Immunostaining with anti-p53 antibody DO-7 was possible in 87 lymphomas, and overexpression of p53 protein was observed in 16 cases (18%). A discrepancy between the results of SSCP and immunostaining was detected on 18 tumor samples. Two cases with mutations in the gene showed no altered protein expression and 16 cases overexpressed p53 protein had no point mutations. In these cases, the possibility that mutations occur outside the exons studied has been tested and the entire coding sequence analyzed. Only one case showed a mutation in exon 10, and we found two cases carrying a polymorphism in exon 4 and in intron 10. We conclude that mutations in p53 occur mainly in high-grade B-cell NHLs. Although not limited to a specific subtype of lymphoma, they may be rare in Hodgkin's disease and in low-grade lymphomas. The discrepancies between overexpression and presence of mutations suggest (1) the existence of another mechanism to stabilize the p53 protein, and (2) that the immunohistochemistry cannot be used to predict mutations in the gene.
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PMID:Correlation between mutations in p53 gene and protein expression in human lymphomas. 913 10

About one fourth of patients with Hodgkin's disease relapse after therapy. The mechanisms that lead to resistance to treatment in these patients are poorly understood. The authors describe the differential protein expression of p53, proliferating cell nuclear antigen (PCNA), and p21 at initial presentation and relapse, and discuss their role in disease progression and resistance to therapy. Thirty-four patients with Hodgkin's disease who had relapsed after standard chemotherapy and radiotherapy regimens were assessed for the expression of p53 protein, PCNA, and p21 protein (waf/cip 1). In 14 of these cases, sequential biopsies performed both at presentation and at relapse were available for the study. Seventy-five percent of the cases were positive for the p53 protein. Tumors at relapse had higher p53 and PCNA scores than those at initial presentation. In the paired samples, a significant increase was noted in the number of p53 and PCNA-positive cells and in the intensity of staining with p53 antibody. Six of seven paired samples tested for p21 showed an increased p21 expression at relapse. These results suggest that, at relapse, Reed-Sternberg (RS) cells and their variants positive for p53, PCNA, and p21 are increased in number and individually have an increased expression of p53, PCNA, and p21 proteins. These findings suggest that therapy failure and relapse may, at least in part, be associated with altered p53, p21, and PCNA pathways. HUM PATHOL 28:549-555. This work was carried out during an exchange fellowship program at the National Cancer Institute, Bethesda. There are no restrictions on its use
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PMID:A study of p53 protein, proliferating cell nuclear antigen, and p21 in Hodgkin's disease at presentation and relapse. 915 3

The occurrence of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) appearing in the same individual indicates a closer relationship between the 2 diseases than previously believed. The purpose of our study was to analyze cases of HD and NHL in a defined population clinically, histopathologically and immunohistochemically to look for similarities indicating a common cellular origin. Between 1974 and 1994, 77 individuals were identified from the Swedish Cancer Registry and the National Health Care Programme for HD as potentially having both diagnoses. Thirty-two patients who had both HD and NHL were available for histo-pathological re-examination and immunohistochemical staining with CD30, CD15, LMP, p53, CD45 (LCA), CD3, CD45R0 (UCHL-1), L26, MB2 and CD45R (4KB5). The most common relation was HD preceding a high-grade malignant NHL (16 of 32 patients), unexpectedly often of T-cell phenotype (7 of 16 patients). The next common association was NHL of B-CLL type followed by HD (7 of 32 patients). At clinical presentation, the first lymphoma did not differ from lymphomas not associated with a second lymphoma, whereas the second one often appeared with a disseminated and aggressive clinical form. There was a significant correlation between the expression of p53 and LMP in first and second lymphomas. CD3 antibody was frequently expressed both in HD and NHL, whereas positivity for B-cell-related antibodies, CD30, CD15 and CD45R0, was less frequent and generally lower than previously described. The occurrence of HD and NHL in an individual is unusual. Tumour biological features common to both HD and NHL may indicate a similar cellular origin, regardless of the time interval between the diagnoses, and may contribute to the understanding of the pathogenesis of lymphoma.
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PMID:Patients suffering from both Hodgkin's disease and non-Hodgkin's lymphoma: a clinico-pathological and immuno-histochemical population-based study of 32 patients. 917 1

Mantle-cell lymphoma comprises 2%-10% of all non-Hodgkin's lymphomas (NHLs). Patients present with generalized disease, and have a poor prognosis. Three different histologic patterns (mantle zone, nodular, and diffuse) and three different cytological variants (classical, blastic, and pleomorphic) have been described. The phenotype (strong surface IgM, CD5+, CD10-, CD23-, cyclin D1+ and B-cell markers+) is remarkably constant. Dependent on the methods used (PCR, Southern blot analysis, and cytogenetics) a t(11;14) can be detected in approximately 35%-66% of cases. Using FISH analysis, possibly almost all cyclin D1-expressing MCLs carry this translocation, indicating that a substantial part of these translocations are missed by conventional methods. This has been confirmed by DNA fiber FISH analysis by which the breakpoints could be accurately mapped over a 220 kb region centromeric of the cyclin D1 gene. Additional genetic abnormalities involve breakpoints and deletion at the 3' end of the cyclin D1 gene, numerical chromosomal aberrations, mutations in p53, and deletions of p16. These may be associated with tumor progression. Owing to the translocation t(11;14), the cyclin D1 gene is activated. At the RNA level, approximately 90% of MCLs show overexpression. This corroborates immunohistochemistry on paraffin tissue sections. Since expression of cyclin D1 in normal lymphoid cells is very low to undetectable, and only hairy-cell leukemia and very few other B-cell lymphomas show expression, immunohistochemistry for cyclin D1 provides an excellent marker for MCL. In hairy-cell leukemia, expression is moderate and cannot be explained by chromosomal translocation.
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PMID:Bcl-1/cyclin D1 in malignant lymphoma. 920 53

This study investigates the human oncoprotein MDM2, which interferes with regulation of cell division and apoptosis. Fifteen mixed-type follicular non-Hodgkin's lymphomas, ten leukaemias, two hepatocellular carcinomas, one osteosarcoma, and ten normal cell lines (fibroblasts, osteoblasts, mesothelium, peripheral lymphocytes) were tested for MDM2 expression and MDM2 gene mutation by reverse transcriptase-polymerase chain reaction (RT-PCR), immunocytochemistry, and nucleotide sequence analysis. Two follicular lymphomas, three leukaemias, both hepatocellular carcinomas, and the osteosarcoma sample showed transcription of the activated MDM2 gene. These samples lacked amplified MDM2 genes and carried mis-sense, non-sense and frame-shift mutations in a zinc finger region of MDM2, altering the amino acid sequence or causing premature termination of transcription. The mis-sense mutations were found in tumour cells that showed significant accumulation of MDM2 and lack of nuclear p53. Non-sense mutations and frame-shift mutations were found in tumours lacking MDM2 proteins. The mutations may affect the biological properties of MDM2 proteins.
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PMID:Point mutations and nucleotide insertions in the MDM2 zinc finger structure of human tumours. 922 42

A novel GM-CSF-dependent myeloid cell line, OHN-GM, was established from a patient who developed acute myelogenous leukaemia (AML) as a consequence of myelodysplastic syndrome (MDS). As the patient had previously received cytotoxic chemotherapy for Hodgkin's disease, the MDS and AML were probably related to such therapy. Sequential karyotypic analysis established a del(5q) as the initial cytogenetic abnormality. Additional alterations, including t(10;13)(q24;q14), had developed subsequently during disease progression. Southern blot analysis of OHN-GM cells suggested deletion of one allele of the IRF-1 gene, although no aberrant transcripts were detected. Fluorescence in situ hybridization analysis revealed the deletion of the Rb gene due to the t(10;13)(q24;q14) translocation, and Western blot analysis demonstrated the absence of Rb protein in OHN-GM cells. Finally, the OHN-GM cells exhibited two missense point mutations in highly conserved regions of the p53 gene. These observations suggest that a multistep process, involving alterations of Rb and p53 genes, may have contributed to the patient's disease development and progression. To our knowledge, OHN-GM is the first cell line derived from a therapy-related AML. These cells may aid the investigation of leukaemogenesis as well as the biology of secondary leukaemia.
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PMID:Alterations of p53 and Rb genes in a novel human GM-CSF-dependent myeloid cell line (OHN-GM) established from therapy-related leukaemia. 926 38

Ataxia-telangiectasia (A-T) is a recessive multi-system disorder caused by mutations in the ATM gene at 11q22-q23 (ref. 3). The risk of cancer, especially lymphoid neoplasias, is substantially elevated in A-T patients and has long been associated with chromosomal instability. By analysing tumour DNA from patients with sporadic T-cell prolymphocytic leukaemia (T-PLL), a rare clonal malignancy with similarities to a mature T-cell leukaemia seen in A-T, we demonstrate a high frequency of ATM mutations in T-PLL. In marked contrast to the ATM mutation pattern in A-T, the most frequent nucleotide changes in this leukaemia were missense mutations. These clustered in the region corresponding to the kinase domain, which is highly conserved in ATM-related proteins in mouse, yeast and Drosophila. The resulting amino-acid substitutions are predicted to interfere with ATP binding or substrate recognition. Two of seventeen mutated T-PLL samples had a previously reported A-T allele. In contrast, no mutations were detected in the p53 gene, suggesting that this tumour suppressor is not frequently altered in this leukaemia. Occasional missense mutations in ATM were also found in tumour DNA from patients with B-cell non-Hodgkin's lymphomas (B-NHL) and a B-NHL cell line. The evidence of a significant proportion of loss-of-function mutations and a complete absence of the normal copy of ATM in the majority of mutated tumours establishes somatic inactivation of this gene in the pathogenesis of sporadic T-PLL and suggests that ATM acts as a tumour suppressor. As constitutional DNA was not available, a putative hereditary predisposition to T-PLL will require further investigation.
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PMID:Clustering of missense mutations in the ataxia-telangiectasia gene in a sporadic T-cell leukaemia. 928 6

Previous studies have shown that in non-Hodgkin's lymphomas and others neoplasms, tumoral progression, treatment response, and outcome are related to the expression of different oncogenic and tumor suppressor proteins. This study aimed to determine the prognostic significance of the expression of p53, bcl2, retinoblastoma protein (Rb), Ki67, CD15, and latent membrane protein 1-Epstein-Barr Virus (LMP1-EBV) proteins in Hodgkin's disease. A retrospective study was performed on 140 patients collected at the 11 participating centers belonging to the Spanish Collaborative Group for the Study of Hodgkin's Disease. A highly sensitive immunohistochemical method with previous microwave-induced antigen retrieval technique was used for the demonstration of the above-mentioned proteins. A Cox's multivariate analysis was performed to evaluate the impact of the variables in the overall survival, together with a logistic regression model for the achievement of complete remission. Univariate statistical analysis confirmed the prognostic significance of the alredy known clinical parameters: stage, age over 60 years, and B symptoms. High proliferation index (Ki67) and loss of Rb expression were also found to be adverse prognostic factors influencing respectively lower overall survival and failure to achieve complete remission. Multivariate analysis confirmed the independent significance of these two parameters and additionally identifies LMP1-EBV expression as a favorable prognostic marker, in relation with overall survival. Histopathological type, p53, bcl2, and CD15 expression lack significant influence on the outcome of this series. The progression of the disease or the response to treatment in HD patients is the consequence of the interrelationship of different factors, among which LMP1 expression, loss of Rb, and high growth fraction seems to play a more relevant role.
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PMID:Adverse clinical outcome in Hodgkin's disease is associated with loss of retinoblastoma protein expression, high Ki67 proliferation index, and absence of Epstein-Barr virus-latent membrane protein 1 expression. 931 Apr 94

AIDS-related small noncleaved cell lymphoma (AIDS-SNCCL) includes Burkitt's lymphoma (BL) and high-grade B-cell Burkitt-like lymphoma (BLL). Due to the marked polymorphism of AIDS-related non-Hodgkin's lymphomas (AIDS-NHL), the morphologic distinction between these two types of lymphomas is frequently controversial, although it may bear clinical relevance. Although the molecular features of AIDS-BL have been clarified to a certain extent, the genetic peculiarities of AIDS-BLL have not been investigated in detail. In this study we have compared morphologic and genetic features of AIDS-BL and AIDS-BLL in a blind coded fashion. Molecular studies were focused on the genetic lesions known to be implicated in AIDS-NHL, including alterations of c-MYC, BCL-6, p53, deletions of 6q, as well as infection by EBV and HHV-8. Alterations of c-MYC occurred in 10/10 AIDS-BL, whereas they were restricted to 2/10 AIDS-BLL (P < 0.01). Mutations of p53 were present in 5/10 AIDS-BL, whereas they were consistently absent among AIDS-BLL (n = 10; P < 0.05). Infection by EBV occurred in 30% of both AIDS-BL and AIDS-BLL. Rearrangements of BCL-6, deletions of 6q and infection by HHV-8 scored consistently negative in both AIDS-BL and AIDS-BLL. Based on the genetic lesions tested, the molecular profile of AIDS-BLL appears to be closer to that of AIDS-related diffuse large cell lymphoma (AIDS-DLCL) than to that of AIDS-BL. In contrast to AIDS-BLL however, AIDS-DLCL carried rearrangements of BCL-6 in a fraction of cases (2/9). This study, the largest of its kind reported so far, suggests that AIDS-BL and AIDS-BLL have a different molecular pathogenesis and that characterization of genetic lesions may help to distinguish between these two lymphomas.
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PMID:Genetic heterogeneity of AIDS-related small non-cleaved cell lymphoma. 933 31


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