Development of virus-accelerated thymic lymphoma in AKR mice

The progression of prelymphoma cells (PLC) in the bone marrow to lymphoma cells (LC) in the thymus in the presence of the lymphomagenic retrovirus SL3-3c was studied in a model system of virus-accelerated thymic lymphoma in AKR/J mice. On the average, a single LC appears in the thymus 30 days after the neonatal ip inoculation of SL3-3c virus; 50 days later, thymic lymphoma is clinically detectable. PLC in the bone marrow and oncogenic virus in the thymus are continuously present during this period before lymphoma develops. Biologically active oncogenic virus in the thymus increases as the animal nears the time of lymphoma development. Intrathymic inoculation, but not ip inoculation, of SL3-3c virus results in accelerated thymic lymphoma in 4- to 6-week-old AKR mice. PLC defined as a population of bone marrow-derived thymocyte progenitor cells susceptible to malignant transformation by oncogenic retrovirus after homing to thymus were further studied and characterized. PLC, like normal bone marrow thymocyte progenitors, were found to be radiosensitive and glucocorticoid resistant. Thymocytes of 21- to 28-day-old AKR mice, neonatally inoculated with SL3-3c virus, were studied for PLC. They could not be detected. It is concluded that lymphoma development is the final outcome of a series of events in which bone marrow-derived thymocyte progenitors are transformed after entering the thymus by virus in the thymic environment.