Dominant negative effect of a truncated erythropoietin receptor (EPOR-T) on erythropoietin-induced erythroid differentiation: Possible involvement ofEPOR-T in ineffective erythropoiesis of myelodysplastic syndrome

We isolated a human leukemic cell line UT-7/GM from UT-7, which can differe ntiate into mature erythroid cells with erythropoietin (EPO) treatment, Usi ng this cell line, we examined the effect of a truncated human EPO receptor (EPOR-T) on EPO-induced erythroid differentiation. Transfection studies re vealed that UT-7/GM cells expressing exogenous EPOR-T were likely to underg o apoptosis even in the presence of EPO, In addition, EPOR-T-transfected ce lls could not differentiate into hemoglobin-positive cells after administra tion of EPO, These results suggest that EPOR-T is a negative regulator of E PO-induced anti-apoptosis and EPO-induced erythroid differentiation. The EP OR-T form was expressed in seven of nine cases of myelodysplastic syndrome but not in normal controls. In patients with myelodysplastic syndrome, dysr egulated expression of EPOR-T may cause apoptosis and blockage of erythroid differentiation, resulting in ineffective erythropoiesis. (C) 1999 Interna tional Society for Experimental Hematology. Published by Elsevier Science I nc.