ERYTHROPOIETIN RECEPTOR SIGNALS BOTH PROLIFERATION AND ERYTHROID-SPECIFIC DIFFERENTIATION

Ectopic expression of the erythropoietin receptor (EPO-R) in Ba/F3, an interleukin 3-dependent progenitor cell line, confers EPO-dependent c ell growth. To examine whether the introduced EPO-R could affect diffe rentiation, we isolated Ba/F3-EPO-R subclones in interleukin 3 and ass ayed for the induction of beta-globin mRNA synthesis after exposure to EPO. Detection of beta-globin mRNA was observed within 3 days of EPO treatment, with peak levels accumulating after 10 days. When EPO was w ithdrawn, expression of beta-globin mRNA persisted in most clones, sug gesting that commitment to erythroid differentiation had occurred. Alt hough EPO-R expression also supports EPO-dependent proliferation of CT LL-2, a mature T-cell line, those cells did not produce globin transcr ipts, presumably because they lack requisite cellular factors involved in erythrocyte differentiation. We conclude that the EPO-R transmits signals important for both proliferation and differentiation along the erythroid lineage.