Proliferation and apoptosis-related gene expression in experimental acquired immunodeficiency syndrome-related simian lymphoma

Lymphomas in 10 cynomolgus monkeys infected with a simian immunodeficiency virus (SIVsm) were studied with regard to proliferative activity and apopto sis-related gene expression. All were diffuse large-cell lymphomas, showed mono or oligoclonality and a 9/10 diploid cellular DNA content. Expression of a simian homologue to Epstein-Barr virus (HVMF-1) was shown in nine case s. The lymphomas showed moderate to high proliferative activity by Ki67 imm unostaining and DNA flow cytometry, and a low number of apoptotic cells det ected by TdT-mediated dUTP nick-end labeling (TUNEL). Immunohistochemistry showed abundant tumor infiltrating TIA-1(+) cytotoxic lymphocytes (CTL) and macrophages. Bcl-2, Mcl-1,and also Bar and Bak, but not p53 were demonstra ble in the tumor cells by immunostaining. Our findings suggest a causal rel ationship between HVMF-1 infection and a low apoptotic index of the lymphom as due to the expression of Bcl-2. The apparent inefficient function of tum or-infiltrating CTL could be due to inactivation of CTL and/or resistance o f the lymphoma cells to CTL effects. The tumors showed immunoreactivity for CD18, CD29, and CD49d, bur not for CD11a, mimicking the phenotype of human Epstein-Barr virus (EBV)-related lymphomas. In summary, our observations i ndicate a high similarity between this simian model of acquired immunodefic iency syndrome (AIDS)-related lymphomas (ARL) and human ARL and other immun osuppression-related lymphomas, (C) 1999 by The American Society of Hematol ogy.