Abstract 82: Development of the baboon as an animal model for adult T-cell leukemia/lymphoma

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Background: Adult T-cell leukemia/lymphoma (ATLL) is a T-cell lymphoma that can be found in the blood (leukemia), lymph nodes (lymphoma), or many areas of the body. ATLL has been linked to infection by the human T-cell lymphotropic virus type 1 (HTLV-1). HTLV-1 infects millions of people worldwide. However, less than five percent of individuals with the HTLV-1 will develop HTLV-associated diseases such as ATLL (d'Offay et al. 2007). The simian counterpart of HTLV-1 is the Simian T-cell leukemia virus-1 (STLV-1). STLV-1 is endemic in Old World monkeys including baboons, and has been linked to lymphomas in nonhuman primates (Takemura et al 2002, Saksena et al. 1994, d'Offay et al. 2007). Lymphoma is the most common neoplasm of nonhuman primates (Hubbard et al. 1993, Hunt et al 1983). Some baboons naturally infected with STLV-1 develop leukemia/lymphoma that shares clinical and pathological features with human ATLL (Hubbard et al. 1993, Schatzl et al 1993). At Texas Biomed we have a large population of pedigreed baboons, some are infected with STLV-1. The aim of our study was to investigate the relationship between STLV-1 infection and ATLL in a captive baboon colony and to develop the baboon as a model to study the link between retroviruses and ATLL. Methods: We reviewed the pathology reports of 135 baboons that went for necropsy during the years of 1991-2014 that had a diagnosis of lymphosarcoma which involved non-lymphoid organs. Results: The most common clinical finding was generalized lymphadenopathy and weight loss. Microscopic examination indicated that in most animals neoplastic cells were found in most organs. Organs were effaced by a uniform population of small, well differentiated lymphocytes with occasional mitoses. Also, the lymph nodes and the splenic white pulp contained increased numbers of lymphocytes with multifocal disorganization of the preexistent architecture. Other than the lymphoid organs, the lungs were the organ involved most (>90%). Other organs involved included kidney (56%), liver (60%), heart (46%), skin (9%) and eye (3%). Using Immunohistochemistry the neoplastic cells showed strong immunoreactivity for CD3 but were negative for CD79a and CD68. Conclusions: Due to the fact that baboons naturally infected with STLV-1 develop leukemia/lymphoma that shares clinical and pathological features with human ATLL, we recommend using the baboon as a useful model for studying the mode of transmission and therapies for ATLL. Further studies: We have initiated a study on the role of genetics in the pathogenicity STLV-1. References: Hubbard GB, Mone JP et al.1993; 43(4):301-9. d'Offay JM, Eberle R et al. 2007;57(1):105-14. Takemura T, Yamashita M et al. 2002;76(4):1642-8. Saksena NK, Herve V et al.1994;198(1):297-310. Hunt RD, Blake BJ et al.1983; 80(16):5085-9. Schatzl H, Tschikobava M et al.1993;7 Suppl 2:S86-92. Courgnaud V, Van Dooren S et al. 2004;78(9):4700-9. Citation Format: Thushari Alahapperuma, James N. Mubiru, Alice Yang, Maggie Garcia-Forey, Edward J. Dick, Michael Owston, Robert E. Shade. Development of the baboon as an animal model for adult T-cell leukemia/lymphoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 82. doi:10.1158/1538-7445.AM2014-82