The general objective of this research project is to study the pathogenesis of AIDS-associated lymphoproliferative disorders including non-Hodgkin lymphoma (AIDS-NHL), Hodgkin disease (Aids- HD) and chronic lymphocytic leukemia (AIDS-CLL). We have identified clonal B-cell populations which are detectable in the lympho nodes of AIDS patients affected by the lymphadenopathy syndrome (LAS) and may represent premalignant populations. We have also determined that c-myc oncogene activation and Epstein-Barr Virus (EBV) infection are associated with AIDS-NHL development. Based on these findings the following lines of research will be pursued: 1) Isolation of clonal B-cell populations and characterization for stage of differentiation, growth requirements, presence and expression of EBV sequences, antibody production and reactivity against relevant viruses (HTLV-I, HTLV-II, HIV, CMV, EBV); 2) Molecular analysis of rearranged and unrearranged c-myc oncogene loci in AIDS-NHL to gain insight into the mechanism of activation; 3) testing the biological effects of c-myc oncogene introduced into the clonal B-cell population isolated in 1); 4) analysis of the role of EBV infection in EBV-positive AIDS-NHL cases; 5) molecular analysis of AIDS-HD and AIDS-CLL for clonality, presence of activated oncogenes (c-myc) and presence of relevant viral sequences (HTLV-I, HTLV-II, HIV, CMY, EBV).
