INTERFERON-ALPHA INHIBITS ERYTHROPOIETIN-INDUCED PROLIFERATION, BUT NOT DIFFERENTIATION, AND RESTRICTS ERYTHROLEUKEMIA DEVELOPMENT

The immature erythroid cell line J2E responds to erythropoietin (Epo) by proliferating and terminally differentiating into hemoglobin-synthe sizing red blood cells. These cells produce a rapid, fatal erythroleuk emia in mice characterized by hepatosplenomegaly and severe anemia. Th e aim of this study was to investigate the effects of murine interfero ns-alpha (MuIFN-(alpha) on J2E cells in vitro and in vivo, Here we sho w that in culture MuIFN-alpha inhibited the Epo-induced proliferation of J2E cells but did not interfere with differentiation. When mice wit h J2E erythroleukemias were treated with MuIFNs in vivo, an extension of their life span was observed, Moreover, numerous necrotic lesions o f infiltrating leukemic cells were detected in the spleens of these mi ce, Finally, ex vivo treatment of leukemic bone marrow cells with Epo and MuIFNs delayed mortality even further. It was concluded that MuIFN s (1) suppressed the proliferation of J2E cells in vitro but did not a ffect Epo-induced differentiation, and (2) inhibited the progress of e rythroleukemias, especially in combination with Epo.