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.