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.
Department of Medicine, Jichi Medical School, Tochigi, Japan.
R
R
Shimizu
N
N
Komatsu
Y
Y
Miura
D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D004920:Erythropoiesis / Q000502:physiology*; D004921:Erythropoietin / Q000494:pharmacology*; D005799:Genes, Dominant; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000473:pathology* / Q000503:physiopathology; D017467:Receptors, Erythropoietin / Q000819:agonists / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured
D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D004921:Erythropoietin