title: Emerging pathways in the development of AIDS-related lymphomas.
abstract: The clinicopathological range of AIDS-related non-Hodgkin lymphomas (NHLs) includes systemic lymphomas, primary central-nervous-system lymphomas, primary effusion lymphoma, and plasmablastic lymphoma of the oral cavity. Most AIDS-related NHLs belong to one of three categories of high-grade B-cell lymphomas: Burkitt's lymphoma, centroblastic lymphoma, and immunoblastic lymphoma. The pathological heterogeneity of AIDS-related NHL reflects the heterogeneity of their associated molecular lesions. In AIDS-related Burkitt's lymphoma, the molecular lesions involve activation of c-MYC, inactivation of p53, and infection with Epstein-Barr virus (EBV). AIDS-related immunoblastic lymphomas infected with EBV are characterised by frequent expression of latent membrane protein 1-an EBV oncoprotein. The biological heterogeneity of AIDS-related NHLs is highlighted by their histogenetic differences; AIDS-related NHLs are related to distinct B-cell subgroups (eg, germinal-centre or post-germinal-centre B cells). The phenotypic pattern of AIDS-related Burkitt's lymphomas and systemic AIDS-related centroblastic lymphomas closely reflects that of B cells in germinal centres. Conversely, the phenotype of AIDS-related immunoblastic lymphomas and AIDS-related primary effusion lymphomas reflects post-germinal-centre B cells in all cases. Despite their clinicopathological, genetic, and phenotypic heterogeneity, most lymphomas in patients with AIDS carry somatic mutations of immunoglobulin and BCL-6 genes. However, the somatic hypermutation mechanism functions aberrantly in a significant proportion of AIDS-related NHLs, causing the mutation of many genes, and possibly favouring chromosomal translocation, which may be a powerful contributor to malignant transformation. New molecular and virological evidence of such pathways and a greater knowledge of other biological features of AIDS-related NHLs may lead to new targets for pathogenetically and biologically oriented therapies.
authors.affiliation: Centro di Riferimento Oncologico-IRCCS, Aviano, Italy. acarbone@cro.itc
authors.forename: Antonino
authors.initials: A
authors.lastname: Carbone
mesh_terms: D002051:Burkitt Lymphoma / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000821:virology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D004268:DNA-Binding Proteins / Q000235:genetics; D020031:Epstein-Barr Virus Infections / Q000150:complications; D016259:Genes, myc; D016158:Genes, p53; D006566:Herpesviridae Infections / Q000150:complications; D019288:Herpesvirus 8, Human; D006801:Humans; D016483:Lymphoma, AIDS-Related / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000821:virology; D016400:Lymphoma, Large-Cell, Immunoblastic / Q000235:genetics / Q000276:immunology / Q000821:virology; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases