Proliferation and Apoptosis-Related Gene Expression in Experimental Acquired Immunodeficiency Syndrome-Related Simian Lymphoma

• Published in: Blood 1999-02, Vol.93 (4), p.1364-1371
• Main Authors: Castaños-Vélez, Esmeralda, Heiden, Thomas, Ekman, Marianne, Lawrence, Joseph, Biberfeld, Gunnel, Biberfeld, Peter
• Format: Article
• Language: English
• Subjects: Medicin och hälsovetenskap
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V93.4.1364.404k19_1364_1371

Lymphomas in 10 cynomolgus monkeys infected with a simian immunodeficiency virus (SIVsm) were studied with regard to proliferative activity and apoptosis-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 cases. The lymphomas showed moderate to high proliferative activity by Ki67 immunostaining and DNA flow cytometry, and a low number of apoptotic cells detected 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 Bax and Bak, but not p53 were demonstrable in the tumor cells by immunostaining. Our findings suggest a causal relationship between HVMF-1 infection and a low apoptotic index of the lymphomas due to the expression of Bcl-2. The apparent inefficient function of tumor-infiltrating CTL could be due to inactivation of CTL and/or resistance of the lymphoma cells to CTL effects. The tumors showed immunoreactivity for CD18, CD29, and CD49d, but not for CD11a, mimicking the phenotype of human Epstein-Barr virus (EBV)–related lymphomas. In summary, our observations indicate a high similarity between this simian model of acquired immunodeficiency syndrome (AIDS)-related lymphomas (ARL) and human ARL and other immunosuppression-related lymphomas.