THROMBOPOIETIN SUPPORTS IN-VITRO ERYTHROID-DIFFERENTIATION VIA ITS SPECIFIC RECEPTOR C-MPL IN A HUMAN LEUKEMIA-CELL LINE

Thrombopoietin (TPO) acts on megakaryopoiesis and erythropoiesis in vi tro and in vivo. We isolated a novel subline, UT-7/GMT, from the human leukemia cell line UT-7/GM (N. Komatsu, et al., Blood, 89: 4021-4033, 1997), A small population of UT-7/GM cells positively stained for hem oglobin (Hb) after a 7-day exposure to TPO, More than 50% of TPO-treat ed UT-7/GMT cells positively stained for Hb, Using UT-7/GMT cells, we examined how TPO promotes hemoglobinization. TPO induced tyrosine phos phorylation of the TPO receptor but not the erythropoietin (EPO) recep tor. There was no competition between TPO and EPO for binding to EPO r eceptor. These findings suggest that TPO has a direct effect on hemogl obinization via a specific receptor on UT-7/GMT cells. Isoelectric foc using demonstrated that TPO induced fetal and adult Hb synthesis, wher eas EPO induced embryonic, fetal, and adult Hb synthesis. Thus, our da ta suggest that TPO has a distinct action on erythropoiesis.