Phenotypic heterogeneity of leukemias associated with friend MuLV infection: Studies on T-cell lymphomas and null cell leukemias in euthymic and thymus-deficient mice

Abstract

The development of leukemia/lymphoma in euthymic and congenitally thymus-deficient (nude) mice infected with Friend murine leukemia virus (Friend MuLV) was investigated; both groups developed fatal leukemias within 2–4 months post-infection but the gross and micropathology of lymphoid organs, coupled with cell-surface marker studies indicated the development of two distinct forms of disease. In euthymic mice one group developed lymphosarcomas manifested by thymoma, hepatosplenomegaly and lymphadenopathy whereas the second group developed splenic leukemias manifested only by hepatosplenomegaly. Analysis of surface markers on spleen cells from mice experiencing lymphosarcomas indicated that the majority of cells were positive for Thy 1.2, Moloney cell surface antigen (MCSA), and viral-coded gp70 and p30 antigens but negative for surface immunoglobulin (sIg). Euthymic mice experiencing splenic leukemias yielded spleen cells negative for Thy 1.2, sIg, and MCSA but positive for gp70 and p30. Nude mice uniformly developed splenic leukemias, spleen cells from which were Thy 1.2, MCSA, gp70 and p30 negative, although the proportion of sIg positive cells was higher than that observed in euthymic mice experiencing splenic leukemias. No correlation between the development of lymphosarcoma vs splenic leukemia and a pattern of ecotropic and/or xenotropic MuLV expression was observed. While ecotropic MuLV expression was equivalent in both euthymic and athymic mice, euthymic mice expressed approx. 10-fold higher levels of xenotropic MuLV than nude mice, however. Collectively the data suggest that infection of mice with Friend MuLV results in the development of two possible forms of disease, lymphosarcoma involving T cells vs splenic leukemia involving B and/or null cells.