Behavior of transplanted large granular lymphocyte leukemia in Fischer 344 rats

The behavior of transplanted large granular lymphocyte leukemia was studied by isogeneic inoculation of 55 young F344 rats. A high percentage of transplants were successful, showing a dose-dependent latent phase followed by weight loss, exponential increase of tumor cells, and widespread infiltration. Serial passage of tumor cells appeared to increase malignancy by decreasing longevity. Grossly, there was splenomegaly, variable lymphadenopathy, and petechial hemorrhages on the lungs, lymph nodes, and brain. Diffuse infiltration of tumor cells caused morphologic changes identical with spontaneous large granular lymphocyte leukemia including splenic lymphoid depletion, hepatocellular necrosis, tumor cell erythrophagocytosis, and femoral medullary endosteal bone proliferation. Clinicopathologic features were also similar to spontaneous large granular lymphocyte leukemia. There was immune-mediated hemolytic anemia and thrombocytopenia, which coincided with development of leukemia, as well as hyperbilirubinemia and elevated serum enzymes, indicative of liver disease. It was concluded that isogeneic transplantation of large granular lymphocyte leukemia is not only highly successful but reproduces the pattern and clinical syndrome of the spontaneous tumor including the important paraneoplastic syndrome of hemolytic anemia and thrombocytopenia.