Shimizu R, Komatsu N, Miura Y
Department of Medicine, Jichi Medical School, Tochigi, Japan.
Exp Hematol. 1999 Feb;27(2):229-33. doi: 10.1016/s0301-472x(98)00048-4.
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.
我们从UT-7中分离出一种人白血病细胞系UT-7/GM，经促红细胞生成素（EPO）处理后，该细胞系可分化为成熟的红细胞。利用该细胞系，我们研究了截短型人EPO受体（EPOR-T）对EPO诱导的红细胞分化的影响。转染研究表明，即使在有EPO存在的情况下，表达外源性EPOR-T的UT-7/GM细胞也容易发生凋亡。此外，给予EPO后，转染了EPOR-T的细胞不能分化为血红蛋白阳性细胞。这些结果表明，EPOR-T是EPO诱导的抗凋亡和EPO诱导的红细胞分化的负调节因子。在9例骨髓增生异常综合征患者中，有7例表达了EPOR-T形式，而正常对照中未表达。在骨髓增生异常综合征患者中，EPOR-T的表达失调可能导致细胞凋亡和红细胞分化受阻，从而导致无效造血。
