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

Deletions of chromosome 6 at band q27 represent the site of a putative novel tumor suppressor gene in non-Hodgkin's lymphomas (NHL) of the immunocompetent host. Although several genetic lesions have been identified in AIDS-related NHL (AIDS-NHL), the involvement of 6q27 loss has not been investigated in this NHL category. In this report, we tested the presence of a 6q deletion at the molecular level in a panel of AIDS-NHL representative of the major histologic types, including AIDS-related small non-cleaved cell lymphoma (AIDS-SNCCL; n = 10), AIDS-related diffuse large cell lymphoma (AIDS-DLCL; n = 13) and AIDS-related anaplastic large cell lymphoma (AIDS-ALCL; n = 3). We report that 6q deletions occur in 5/26 AIDS-NHL tested (19.2%). Notably, 6q deletions do not randomly distribute throughout the spectrum of AIDS-NHL histologic types, but rather selectively cluster with AIDS-DLCL (5/13; 38.4%). Overall, these data add to the notion that the molecular pathogenesis of AIDS-NHL is heterogeneous and that distinct genetic pathways associate with specific histologic categories of AIDS-NHL.
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PMID:Association of 6q deletions with AIDS-related diffuse large cell lymphoma. 866 42

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

Acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin's lymphomas (AIDS-NHLs) consistently derive from B cells, are histologically heterogeneous, and are associated with distinct molecular pathways depending upon histology. Recently, it has been proposed that inactivating mutations of the bax death agonist may contribute to the pathogenesis of human tumors. In particular, among B-cell malignancies, BAX mutations have been detected at a certain frequency in Burkitt lymphomas. This study is aimed at defining the status of the BAX gene throughout the clinicopathologic spectrum of AIDS-NHL (n = 54), including AIDS-related Burkitt lymphoma (n = 14), AIDS-related Burkitt-like lymphoma (n = 8), AIDS-related diffuse large cell lymphoma (n = 15), AIDS-related primary central nervous system lymphoma (n = 6), and AIDS-related primary effusion lymphoma (n = 11). All 6 BAX exons and flanking sequences were subjected to mutational analysis by polymerase chain reaction-single strand conformation polymorphism followed by DNA direct sequencing of positive cases. Mutations of BAX among AIDS-NHL were restricted to a cell line of AIDS-related primary effusion lymphoma, which harbored a frameshift mutation causing the introduction of a proximal stop codon. All other AIDS-NHL displayed wild-type BAX alleles. In order to investigate whether BAX inactivation in AIDS-NHL may occur through mechanisms other than gene mutation, bax protein expression was investigated by Western blot analysis or immunohistochemistry in selected cases. All AIDS-NHL analyzed expressed normal bax proteins. Overall, this study indicates that deregulation of apoptotic control in AIDS-NHL is not caused by BAX alterations. Genes Chromosomes Cancer 27:177-182, 2000.
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PMID:Mutation of BAX occurs infrequently in acquired immunodeficiency syndrome-related non-Hodgkin's lymphomas. 1061 6

AIDS-related non-Hodgkin lymphomas (AIDS-NHL) consistently derive from B-cells and are characterized by extreme clinical aggressiveness. At histological level, AIDS-NHL are classified as AIDS-related Burkitt's lymphoma (AIDS-BL), AIDS-related diffuse large cell lymphoma (AIDS-DLCL) and AIDS-related primary effusion lymphoma (AIDS-PEL). The role of cytokines in the pathogenesis and management of AIDS-NHL has been studied to a certain extent. Production of large quantities of human IL-10 occurs frequently in AIDS-BL and correlates with latent EBV infection of the tumor clone. Lesser amounts of the cytokine are released in EBV negative cases. The pathogenetic role of IL-10 in AIDS-BL is suggested by the observation that IL-10 antisense oligonucleotides inhibit proliferation of the lymphoma. A significant fraction of AIDS-BL cell lines produce TNFbeta. Among AIDS-NHL, the release of TNFbeta appears to be specific for AIDS-BL. The pathogenetic relevance of TNFbeta in lymphomagenesis is suggested by the observation that some BL cell lines use TNFbeta as an autocrine growth factor. Some cases of AIDS-BL, particularly those carrying EBV infection, also secrete IL-6, IL-7 and IL-12. With respect to AIDS-DLCL, many cases express the IL-6R, rendering these cells responsive to the paracrine stimulation by the IL-6 produced by nearby T-cells, macrophages and endothelial cells which are frequently abundant in these tumor samples. The tumor clone itself, however, generally fails to release IL-6. AIDS-PEL is characterized by secretion of large amounts of IL-6 and IL-10. Some PEL cases also release oncostatin M. Apart from human IL-6, PEL also express viral IL-6, which is encoded by the HHV-8 genome. The biological relevance of both IL-6 and IL-10 in PEL proliferation and growth has been recently clarified in vitro and in vivo. Overall, these data suggest that activation of different cytokine loops clusters with different clinico-pathologic categories of AIDS-NHL and may represent the potential target of novel therapeutic strategies.
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PMID:The role of cytokines in the pathogenesis and management of AIDS-related lymphomas. 1095 68