MOLECULAR EPIDEMIOLOGY OF AIDS-ASSOCIATED LYMPHOMA

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DESCRIPTION (adapted from the Abstract): Non-Hodgkin's B-cell lymphoma is seen in greatly-elevated frequency in the acquired immunodeficiency syndrome (AIDS) and in infection with the human immunodeficiency virus (HIV). In this application, the Principal Investigator proposes studies to elucidate the molecular epidemiology of AIDS-lymphoma. In preliminary work, the Principal Investigator found that elevated serum levels of sCD23, as well as elevated levels of other immune system molecules (IgE, sCD27), precede the appearance of AIDS-lymphoma. Also, the elevated levels of sCD23 seen to precede AIDS-lymphoma may be due to the production of this molecule by tumor cells. In the proposed studies, the Investigator and associates will test the hypotheses that the over-expression of sCD23 (and other molecules) that precedes AIDS-lymphoma reflects: (1) immune dysfunction leading to B-cell hyper-activation and enhanced Ig isotype switching, perhaps contributing to the c-myc:Ig gene chromosomal translocation commonly seen in this cancer, or alternatively, (2) the production of these substances (sCD23 and other molecules) by the lymphoma cells themselves, or (3) reactivation of EBV infection. Also, they will examine the predictive value of the expression of these molecules for AIDS-lymphoma, and the expression of these molecules in lymphoma not associated with HIV infection, including African endemic Burkitt's lymphoma. Their specific aims are to: (1) define the pattern of expression of sCD23 prior to the emergence of AIDS-lymphoma; (2) determine/confirm which immune system molecules, other than sCD23, are elevated in those who develop AIDS-lymphoma; (3) determine if the measurement of serum levels of molecules other than sCD23 provides additional information for predicting the appearance of AIDS-lymphoma; and (4) determine if sCD23 or other immune system molecules are elevated in non-Hodgkin's B-cell lymphoma not associated with HIV infection, or in AIDS-lymphoma in hemophiliacs. The accomplishment of these specific aims will add valuable new information to our understanding of the molecular epidemiology of AIDS-lymphoma, as well as the role of immune dysfunction in the generation and growth of this cancer.