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)

Despite a common origin from mature lymphoid cells, non-Hodgkin lymphomas (NHL) represent a surprisingly heterogeneous group of lymphoid malignancies whose classification is continuously being remodeled. The most recent proposal, the Revised European-American classification, introduces pathogenetic features among the classification criteria. In this respect, knowledge of the molecular pathogenesis of NHL, which is based upon genetic lesions leading to activation of proto-oncogenes (e.g. BCL-1, BCL-2, BCL-6, c-MYC) or disruption of tumor suppressor genes (e.g. p53), is becoming increasingly relevant for the clinician. These lesions combine into multiple molecular pathways which are selectively associated with distinct NHL types. Thus, for example, rearrangements of BCL-1, BCL-2, BCL-6, and c-MYC ar the genetic hallmarks of mantle cell, follicular, diffuse large cell, and Burkitt's lymphoma, respectively. Overall, from clinical perspective, NHL genetic lesions serve three purposes: a) they assist and complement histologic diagnosis; b) they provide a molecular marker with prognostic relevance; c) they allow evaluation of minimal residual disease through highly specific and highly sensitive technologies.
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PMID:Molecular pathogenesis of non-Hodgkin lymphoma: a clinical perspective. 856 91

Limited information is current available on the molecular and immunophenogenotypic characteristics of CD30-positive anaplastic large cell (ALC) lymphomas occurring in human immunodeficiency virus (HIV)-infected individuals. To address this issue, the authors have undertaken a combined analysis of these lymphomas in a comparison with other Epstein-Barr virus (EBV)-associated tumors in the setting of HIV infection. Twenty-one AIDS-related lymphomas, including five CD30-positive ALC and 11 small noncleaved cell (SNCC) lymphomas, and five Hodgkin's disease (HD) specimens were characterized regarding the immunophenogenotypic features, the frequency and subtype distribution of EBV (as defined by in situ hybridization [ISH], Southern blot, and a polymerase chain reaction [PCR] amplification of the EBV nuclear antigen-2 [EBNA-2] region) antigen expression (latent membrane protein-1 [LMP-1], EBNA-2, and for alterations of the tumor suppressor gene p53. Combined immunophenotypic and immunogenotypic analyses showed a derivation from anomalously matured B cells in four of five CD30-positive ALC lymphomas, whereas SNCC showed features of mature B cells; no evidence of immunoglobulin or TCR gene rearrangement could be obtained in HD cases. Combined ISH and Southern blot analyses revealed that EBV was more strictly associated with HD (five of five) and CD30-positive ALC lymphomas (four of five) than with SNCC lymphomas (four of 11). EBV-positive samples from CD30-positive ALC lymphomas carried type 1 EBV (two of two specimens tested), whereas both EBV subtypes were observed in SNCC lymphomas and HD samples. All three forms of viral latent gene expression were found in the EBV positive CD30-positive ALC lymphomas. SNCC specimens did not express LMP-1 or EBNA-2, whereas HD specimens expressed LMP-1 (four of five tested) but no EBNA-2. Immunostaining for ZEBRA was consistently negative. HHV-6 DNA sequences were detected by PCR in one SNCC of the 19 specimens analyzed. Three out of five CD30-positive ALC lymphoma specimens and six of 10 SNCC showed nuclear staining for p53. No mutation was detected in any of the three CD30-positive Alc lymphoma analyzed, whereas an aberrant SSCP pattern was found in all the four SNCC samples tested. At variance with SNCC lymphomas, AIDS-related B-cell CD30- positive ALC lymphomas are strictly associated with EBV infection and may also express the broad lymphoblastoid cell line-like (LMP-1-positive, EBNA-2-positive) pattern, and lack p53 genetic lesions. Unlike EBV, HHV-6 probably does not represent a relevant factor involved in the pathogenesis of CD30-positive ALC and other HIV related lymphomas.
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PMID:Immunophenotypic and molecular analyses of acquired immune deficiency syndrome-related and Epstein-Barr virus-associated lymphomas: a comparative study. 861 54

p53, a tumor suppressor gene, is frequently mutated in sporadic human cancer, and inherited mutations in p53 predispose to the early onset of cancer. p53 mutations occur frequently in sporadic lymphoma, and, in mice deficient for p53, lymphoma is the most common type of malignancy. Families with an increased incidence of lymphoma have been described, suggesting an inherited predisposition to lymphoma in these circumstances. To determine whether the predisposition to lymphoma in these families results from germline mutations in p53, we analysed exons 4-11 of the p53 gene in 35 individuals from 19 lymphoma-prone kindreds. We found no germline p53 mutations in any of the individuals tested. However, p53 expression assessed by immunohistochemistry, which suggests mutation, was observed in 35% of the tumor samples from the familial Hodgkin's disease cases and in 13% of the familial non-Hodgkin's lymphoma cases. These results suggest that p53 mutations do not play a critical role in heritable susceptibility to lymphoma. p53 may act by different, non-mutation related mechanisms in this setting, or be involved in late events in the pathogenesis of these tumors.
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PMID:Absence of germline p53 mutations in familial lymphoma. 863 26

p21 is induced by and mediates the effects of p53 in response to DNA damage arresting the cell in G1 or G2, by inhibiting multiple cyclin-cyclin-dependent kinases (CDK) or binding to proliferating-cell nuclear antigen (PCNA), respectively. To determine whether p21 mutants occur in tumors we examined DNA from 188 primary non-Hodgkin's B-cell lymphoma (NHL) tumors and 84 chronic myelogenous leukemia samples for mutational changes in the coding region of p21 by single-strand conformation polymorphism (SSCP) analysis and direct sequencing of polymerase chain reaction (PCR)-amplified DNA. We did not find mutations in the coding region in these two tumor types. We identified a polymorphic nucleotide change in codon 31 in which a transversion from C to A substituted amino acid arginine for serine. Three of 188 NHL tumors were homozygous for this change, but they were not identified in 84 CMLs or in 97 normal controls. On the other hand, in one CML case a transition from G to A in codon 64 substituted amino acid threonine for alanine. These data do not indicate that derangements in the coding region of p21 contribute to the initiation and/or progression of these tumors.
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PMID:Absence of somatic changes in p21 gene in non-Hodgkin's lymphoma and chronic myelogenous leukemia. 865 61

AIDS-related non-Hodgkin's lymphomas (AIDS-NHLs) are almost invariably derived from B cells and are grouped into three distinct histologic categories, including small-non-cleaved-cell lymphoma (SNCCL), diffuse large-cell lymphoma (DLCL), and anaplastic large-cell lymphoma (ALCL). In addition, AIDS-NHLs presenting solely as a body cavity effusion are thought to be a peculiar clinicopathologic entity and are defined as body-cavity-based lymphoma (BCBL). At the biologic level, AIDS-related lymphomagenesis is characterized by activation of proto-oncogenes, inactivation of tumor suppressor genes, viral infection of the tumor clone, and deregulated cytokine production. Distinct AIDS-NHL types associate with specific molecular pathways. The first pathogenetic pathway clusters with AIDS-SNCCL, and is characterized by a relatively mild degree of host immunodeficiency. AIDS-SNCCL consistently associates with c-myc rearrangements and p53 inactivation in 100 and 60% of cases, respectively, whereas infection by Epstein-Barr virus (EBV) is restricted to 30% of the cases. Production of high levels of interleukin-10 is an additional peculiar feature of EBV-positive AIDS-SNCCL. The second pathogenetic pathway associates with AIDS-DLCL, which is usually accompanied by marked host immunodeficiency. AIDS-DLCL is characterized by EBV infection in the large majority of cases and by the mutually exclusive presence of bcl-6 rearrangements and c-myc translocations in 40% of the cases. A third pathway characterizes AIDS-BCBL, which associates in virtually all cases with infection by EBV and with the presence of DNA sequences of the recently identified Kaposi sarcoma herpesvirus in the apparent absence of other known genetic lesions. Finally, the pathogenetic features of AIDS-ALCL are still under investigation.
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PMID:AIDS-related non-Hodgkin's lymphomas: molecular genetics, viral infection and cytokine deregulation. 867 42

The recent demonstration that the murine anti-p53 monoclonal antibody PAb248 can identify human p53 in a variety of normal tissues proves that immunohistochemical detection does not necessarily indicate the presence of mutations. PAb248 can detect p53 protein in a cytoplasmic-perinuclear localization, not previously described. The present study presents the expression of this antibody in a series of 34 cases of Hodgkin's disease, comparing it with the antibodies CM1, PAb1801, and PAb240. In all cases, PAb248 showed uniform cytoplasmic-perinuclear staining in small and medium-sized lymphocytes, while it was constantly negative in Hodgkin, Reed-Sternberg (R-S/H) cells, and variants. This pattern of staining was the opposite to that observed with the antibodies CM1, PAb1801, and PAb240, where the staining was nuclear and restricted to the R-S/H cells, with the small lymphocytes being negative. p53 can be found in different conformations and localizations, with the cytoplasmic-perinuclear localization mainly, although not exclusively, being found in normal and reactive tissues and the nuclear localization being mainly expressed by neoplastic cells. These results give further support to the theory that the R-S/H cells are the neoplastic population in Hodgkin's disease, while the surrounding lymphocytes are reactive.
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PMID:Detection of p53 in Hodgkin's disease using the monoclonal antibody PAb248. 868 84

The expression of the apoptosis-regulating genes Bcl-2, Bcl-x, Bax, Mcl-1, and p53 analyzed in 4 cases of human immunodeficiency virus (HIV)-associated Hodgkin's disease, in 36 cases of HIV-related non-Hodgkin's lymphomas (NHLs), and in 109 cases of non-HIV-related NHLs by using immunohistochemistry. HIV-associated Hodgkin's disease samples were positive for all markers. For the HIV-related NHL samples, 36, 66, 88, 100, and 94% of the cases were Bcl-2, Bcl-x, Bax, Mcl-1, and p53 were found to be expressed in 69, 65, 82, 83, and 42%, respectively. No significant differences were observed in Bax and Mcl-1 staining between HIV-unrelated NHLs of B cell and T cell types. In contrast, Bcl-2 was positive in 66/79 (83%) and 10/30 (33%) of B cell and T cell HIV-unrelated NHLs, respectively (P2 < 0.001). Peculiar patterns were observed for hairy cell leukemia (Bax+, Bcl-2+, Mcl-1-) and for anaplastic large cell lymphoma (Bax+, Mcl-1+, Bcl-2-) in HIV-unrelated NHLs. Of interest, all cases with a positive expression of Bax were also found to express either Mcl-1 and/or Bcl-2, suggesting that Mcl-1 and Bcl-2 may counteract the pro-apoptosis function of Bax in vivo by protein-protein interaction within the tumor cell, as demonstrated previously in vitro. These results suggest that apoptosis regulation may have a role in the pathogenesis of some HIV-related and HIV-unrelated NHLs.
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PMID:Immunodetection of apoptosis-regulating proteins in lymphomas from patients with and without human immunodeficiency virus infection. 868 41

Expression of the Epstein-Barr virus (EBV) gene product LMP1 is found in tumour cells in varying proportions of Hodgkin's disease (HD) cases. It is not clear which cellular genes are influenced by EBV in HD. A total of 387 HD cases were tested for differences among LMP1-positive and -negative cases with respect to age, sex, histotype and immunophenotypic parameters (CD2, CD3, CD4, CD15, CD19, CD20, CD21, CD22, CD23, CD25, CD30, CD43, CD45RA, CD45R0, CD70, HLA-DR, T-cell receptor beta-chain, and p53 expression). Comparison of patient age and sex as well as distribution of histotype and tumour cell immunophenotype with published data suggests that the cases in this study are representative of the spectrum of HD in developed countries. LMP1 expression was found in 131/387 HD cases (36.4 per cent) with non-homogeneous distribution among HD histotypes, the mixed cellularity type (HDmc) being most frequently EBV-associated (71/129 cases, 55 percent). No relationship was found to age and sex. Significant phenotypic differences were restricted to the HDmc histotype, where the tumour cells expressed the activation marker CD30 in a larger proportion, and CD20 in a smaller proportion, when harbouring EBV. These results suggest that EBV may influence the tumour cell phenotype in HD.
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PMID:Phenotypic modulation of Hodgkin and Reed-Sternberg cells by Epstein-Barr virus. 869 46

A strong association was found to exist between patterns of lymphoid malignancies and socioeconomic status. B-cell lymphomas and T-acute lymphoblastic leukemia are much more prevalent in developing countries where the chances of acquiring infections especially at a younger age are high. B-cell precursor acute lymphatic leukemia, however, are much more prevalent in the Western world. Many infectious agents are associated with lymphatic malignancies. Epstein-Barr virus is involved in African Burkitt's lymphoma, human immunodeficiency virus-related Burkitt's lymphoma, lymphoproliferative syndrome post-transplantation, and Hodgkin's disease. Other infectious agents which may play a role in lymphoproliferative disorders are human immunodeficiency virus in acquired immune deficiency syndrome-associated lymphoma, human T-lymphotropic virus in adult T-cell lymphoma, Helicobacter pylori in mucosa-associated lymphoid tissue lymphoma, theileriosis in lymphoproliferative syndrome in cattle, Avian leukosis virus in chicken bursal lymphoma, and possibly a bacterial infection in immunoproliferative small intestine disease, potentially reversed by antibiotic therapy. The association between infectious agents and hematologic malignancies may be explained by the creation of large populations of activated cells followed by higher occurrences of 'genetic accidents'. This theory may be reinforced in at least some malignancies with the existence of viral proteins which either have complex relationships with key cellular gene products like p53 and Rb which have roles in cell cycle control, or share common motifs with bc1-2, therefore operating as anti-apoptotic elements. Whenever these genes are deranged, cell deoxysibonucleic acid repair or apoptosis are no longer possible, thereby creating a state of genome instability, increased acquisition of mistakes, and increased chances for malignant transformation.
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PMID:Infectious agents and environmental factors in lymphoid malignancies. 881 40

High risks of lung cancer occur after successful treatment of Hodgkin's disease. In addition to tobacco smoking, other risk factors include radiotherapy, chemotherapy, and immunosuppression, although the relative contributions of each are unknown. We conducted p53 mutational spectrum analysis in second lung cancers after radiation therapy for Hodgkin's disease in the Netherlands and in Ontario, Canada. Lung cancer tissues from 11 patients were analyzed by p53 immunohistochemistry and DNA sequence analysis. All were male cigarette smokers, all received radiation therapy, and six also received chemotherapy. The lung cancers occurred 9.8 years (mean) after treatment. Radiation doses to lung lobes that developed the tumors averaged 5.7 Gy (range, 3.7-11.7 Gy). Sequence analysis showed four missense and two silent p53 point mutations in five patients. There were four G:C-->A:T transitions; three of four mutated deoxyguanines occurred on the coding strand, and one was a CpG site. There were two transversions: one G:C-->C:G and one A:T-->C:G. Despite moderate or heavy smoking histories in all patients, the mutational spectrum appears to differ from usual smoking-related lung cancers in which G:C-->T:A transversions predominate. The absence of G:C-->T:A mutations and the prominence of G:C-->A:T transitions, which are characteristic of radiation and oxidative damage, suggest that radiotherapy might have caused some of the p53 mutations. These data illustrate the potential of mutation analysis to determine causes of human cancer. If confirmed in a larger series, these results imply that some radiation-induced cancers can be distinguished from those caused by other factors.
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PMID:p53 mutations in lung cancer following radiation therapy for Hodgkin's disease. 885 Feb 68


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