Document 2984 DOCN M94A2984 TI Pathogenesis of AIDS associated large cell lymphoma. DT 9412 AU Tsuzuki A; Herndier B; Marsh J; Ng V; Nolan T; Shiramizu B; McGrath M; University of California, San Francisco. SO Int Conf AIDS. 1994 Aug 7-12;10(1):18 (abstract no. 045B). Unique Identifier : AIDSLINE ICA10/94369591 AB OBJECTIVE: The pathogenesis of HIV associated Burkitt's lymphoma probably revolves around dysregulation of the c-myc proto-oncogene. For other AIDS associated lymphomas, particularly the large cell lymphomas (LCL), the pathogenesis is unclear, particularly when some pre-lymphomatous states or even frank lymphomas are polyclonal in nature and can in some cases lack demonstrable EBV. This study examines the phenotype of such lymphomas and viral and cytokine expression with the hopes of unravelling the key events in the early stages of lymphomagenesis in HIV disease. METHODS: A consecutive series of 15 large cell lymphomas and malignant effusions were examined by the following techniques: 1) morphology; 2) 3-color cytofluorometry; 3) frozen section immunohistochemistry; 4) reverse transcriptase PCR followed by Southern blotting (IL-6, IL-6R, IL-10); 5) PCR, Southern blotting and in situ hybridization with an EBV EBER probe. RESULTS AND CONCLUSIONS: Twelve of 15 LCL expressed IL-6R RNA and 11/15 IL-10 RNA, indicating the possibility of Il-6/IL-6R and/or IL-10/IL-10R interactions being important in lymphoma growth. Growth studies with cell lines established from malignant effusions indicate both paracrine IL-6/IL-6R and autocrine (IL-6/IL-6R) growth analogous to what has been observed with human multiple myeloma. Six of 7 studied LCL were composed of CD5 positive B cells, the B cell thought to be important in autoimmunity and known to respond to IL-10 as an autocrine growth factor. Neutralizing antibodies to both IL-6 and IL-10 inhibited proliferations of two newly established AIDS LCL cell lines, suggesting that both IL-6 and IL-10 may play important roles in AIDS lymphomagenesis. Our data (7/15 cases) does not support a consistent role for EBV. DE Antigens, CD/ANALYSIS Blotting, Southern Flow Cytometry Human HIV Infections/*COMPLICATIONS Immunohistochemistry In Situ Hybridization Interleukins/ANALYSIS Lymphoma, AIDS-Related/CHEMISTRY/*GENETICS Lymphoma, Large-Cell/CHEMISTRY/*GENETICS Polymerase Chain Reaction MEETING ABSTRACT SOURCE: National Library of Medicine. NOTICE: This material may be protected by Copyright Law (Title 17, U.S.Code).