BCL-6 IN AIDS-RELATED LYMPHOMAS - PATHOGENETIC AND HISTOGENETIC IMPLICATIONS

AIDS-related non-Hodgkin's lymphomas (AIDS-NHL) are classified into Bu rkitt's lymphoma, diffuse large cell lymphoma (DLCL). and body cavity based lymphoma. The molecular pathogenesis of AIDS-NHL is complex end involves the genetic alteration of several cancer related genes, inclu ding the BCL-6 proto-oncogene. BCL-6 encodes a zinc finger transcripti on factor which is selectively expressed by germinal center (GC) B-cel ls, but not by pre-GC or post-GC B-cells. Genetic alterations of BCL-6 occur frequently among B-cell NHL and comprise gross rearrangements a s well as small mutations of the 5' noncoding region of the gene. Gros s rearrangements of BCL-6 among AIDS-NHL cluster with 20% AIDS-DLCL. C onversely, mutations of the 5' noncoding region of BCL-6 occur at sust ained frequency throughout the clinico-pathologic spectrum of AIDS-NHL and represent the most common genetic alteration presently detectable in these lymphomas. The frequency of BCL-6 mutations, as well as thei r location in the proximity of the BCL-6 regulatory regions, suggest t hat they may play a pathogenetic role in AIDS-related lymphomagenesis. Beside their pathogenetic implications, the occurrence of BCL-6 mutat ions among AIDS-NHL bears histogenetic relevance because BCL-6 mutatio ns are regarded as a marker of B-cell transition through the GC. Thus, it is conceivable that a large fraction of AIDS-NHL is histogenetical ly related to GC or post-GC B-cells. This notion is further confirmed by the observation that AIDS-NHL frequently express the BCL-6 protein, which stains selectively GC B-cells throughout B-cell differentiation .