Friend erythroleukemia revisited.

In 1957, Charlotte Friend described a novel retroviral disease in mice characterized by splenic enlargement, erythroleukemia, and death.1 This rapidly progressive disease, now known as Friend disease, has provided a powerful tool for the study of multistage carcinogenesis. Transformed murine erythroleukemia (MEL) cells, isolated from Friend virus–infected mice, have also provided a versatile model system for the study of erythroblast differentiation and erythropoietin (Epo)-induced signal transduction in vitro. Over the years, Friend disease has provided major insights into the molecular evolution of leukemia, the normal mechanisms of Epo receptor (EpoR) activation and, most recently, the molecular mechanisms of leukemia resistance. In this review, we summarize the molecular insights gained from the study of Friend disease. We focus on recent advances, with a special emphasis on studies of the Friend virus susceptibility locus, Fv2. 2