Proliferation and apoptosis-related gene expression in experimental AIDS-related simian lymphoma.
Int Conf AIDS 1998 Jun 28-Jul 3; 12:25 (abstract no. 11216)
Biberfeld P, Castanos-Velez E, Heiden T, Ekman M, Lawrence J, Tribukait B, Biberfeld G Immunopathology Lab., Karolinska Institute, Karolinska Hospital, Stockholm, Sweden.
A simian analogue to human AIDS was induced in cynomolgus monkeys injected with simian immunodeficiency virus (SIVsm). Approximately 40% of the animals developed disseminated high grade malignant non-Hodgkin lymphoma (sARL). Studies of 24 such lymphomas showed that all were extranodal, high grade malignant, of B-cell origin and included monoclonal as well as polyclonal proliferations. Tumor infiltrating TIA-1+ T lymphocytes and CD68+ macrophages were usually abundant. Expression of a simian homologue to EBV-EBER was demonstrated in 23/24 cases. Ploidy studies showed that these lesions were nealry to diploid (D.I. = 1.0). Apoptosis was an uncommon finding in the tumors and in most of the cases, tumor cells were shown to be highly proliferative as indicated by Ki67 expression and S phase and G2 analysis. The antiapoptotic factors Bcl-2 and Mcl-1 were variably expressed by the tumor cells in most of the cases but mutant p53 was not. However the proapoptotic factors Bax and Bak were usually also demonstrable in the lymphoma cells, suggesting their functional inhibition by Bcl-2. The results suggest a relationship between Bcl-2 expression and EBV infection and a negative correlation between Bcl-2 expression and p53 activation. These tumors showed a high homogeneity regard to extracellular matrix proteins (ECM) and cell adhesion molecules (CAM) expression, displaying strong positivity for beta 1 (CD29) and alpha 4 (CD49d) integrin subunits in the tumor as well as in infiltrating non-tumoral cells but negativity for the beta 2 (CD18), alpha L (CD11a), alpha M (CD11b) and alpha x (CD11c) integrin subunits. The similarity at the molecular level of this simian experimental lymphoma model and human AIDS related lymphomas is strongly emphasised by these findings.
CONCLUSIONS: AIDS-related B-cell lymphomagenesis can be studied experimentally in non-human, SIV infected, primates, particularly with regard to EBV association, lymphoma cell proliferation, expression of antiapoptotic genes and adhesion molecules in relation to decreased immunity.
