Thrombopoietin has a direct effect on erythroid differentiation

The administration of thrombopoietin (TPO) to mice after chemotherapy and total body irradiation not only promotes recovery from chemotherapy-induced thrombocytopenia, but also relieves anemia. In addition, TPO has burst promoting activity (BPA) in vitro. These observations suggest the influence of TPO on erythropoiesis. To elucidate whether TPO has a direct effect on erythroid differentiation, we established a subclone of a human cytokine-dependent cell line UT7, UT-7/GM Hl. UT-7/GM HI is maintained by GM-CSF and can grow in response to erythropoietin (EPO) or TPO. After a 1 week culture in IMDM medium containing 10% FCS in the presence of I U/ml of EPO or 10 ng/ml of TPO, more than 90 % and 45 % of UT-7/GM HI cells, respectively, were dianisidine-stained. Even after treatment of UT7/GM HI cells with up to 100 ng/ml of TPO, the EPO receptor was not tyrosine phosphorylated. These findings suggest that TPO directly induced erythroid differentiation and that the effect was not achieved via an erythropoietin receptor.