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

We isolated a human leukemic cell line UT-7/GM from UT-7, which can differentiate into mature erythroid cells with erythropoietin (EPO) treatment. Using this cell line, we examined the effect of a truncated human EPO receptor (EPOR-T) on EPO-induced erythroid differentiation. Transfection studies revealed that UT-7/GM cells expressing exogenous EPOR-T were likely to undergo apoptosis even in the presence of EPO. In addition, EPOR-T-transfected cells could not differentiate into hemoglobin-positive cells after administration of EPO. These results suggest that EPOR-T is a negative regulator of EPO-induced anti-apoptosis and EPO-induced erythroid differentiation. The EPOR-T form was expressed in seven of nine cases of myelodysplastic syndrome but not in normal controls. In patients with myelodysplastic syndrome, dysregulated expression of EPOR-T may cause apoptosis and blockage of erythroid differentiation, resulting in ineffective erythropoiesis.