Simian AIDS-associated lymphoma in rhesus and cynomolgus monkeys recapitulates the primary pathobiological features of AIDS-associated non-Hodgkin's lymphoma

Non-Hodgkin's lymphomas occur with increased frequency (3-6%) in HIV-infect ed individuals. These AIDS-associated lymphomas (AALs) exhibit characterist ics that distinguish them from lymphomas in the general population. A propo sed model for the pathogenesis of AAL includes the following: (1) Tumorigen esis is multistep; (2) tumors occur in long-term survivors; (3) tumors are of clonal B cell origin; (4) HIV acts early and is an indirect effector (5) tumor cells are infected with EBV; and (6) specific genetic lesions occur in tumor cells. Mane aspects of this process remain to be tested in an anim al model system. Since 1984, necropsy examinations have been performed on m ore than 1000 SIV-infected rhesus and cynomolgus monkeys at the Tulane Regi onal Primate Research Center. Lymphoid malignancies were detected in a prop ortion of SIV-infected animals. These SAIDS-associated lymphomas (SALs) hav e been studied to determine the extent to which their pathological features recapitulate a working model for the pathogenesis of AAL. The results show that lymphomas occur in SIV-infected rhesus macaques at 4% incidence, simi lar to that of AAL, and that the incidence of SAL in cynomolgus macaques is eightfold higher. Analysis of SAL from both species of macaques demonstrat ed significant similarity to the hallmark pathobiological features of AAL, These findings indicate that the HIV-infected human and the SIV-infected ma caque share a common pathobiology and mechanism of lymphomagenesis.