Erythropoietin-induced activation of STAT5 is impaired in the myelodysplastic syndrome
Erythropoietin-induced activation of STAT5 is impaired in the myelodysplastic syndrome
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DOI：
10.1182/blood.v89.5.1690.1690_1690_1700
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发表时间：
1997-03-01
期刊：
影响因子：
20.3
通讯作者：
Lowenberg, B
中科院分区：
文献类型：
--
作者：
Hoefsloot, LH;vanAmelsvoort, MP;Lowenberg, B
骨髓增生异常综合征（MDS）患者体内和体外红细胞生成功能无效，其特征是对促红细胞生成素（Epo）的反应受损。我们更详细地研究了MDS骨髓细胞对Epo的增殖和成熟反应。与正常骨髓（NBM）相比，15例MDS患者骨髓细胞中epo依赖性DNA合成以及诱导GATA-1结合活性严重降低。此外，在MDS细胞培养中，形态学上可识别的红系细胞的出现减少。这些数据表明，Epo依赖的增殖和Epo诱导的分化都受到抑制。为了研究更多Epo信号转导途径的上游事件，我们研究了信号换能器和转录激活因子（STAT） 5的激活。在所有15个MDS样本中，STAT5的激活在对Epo的反应中缺失或被严重抑制，相反，白细胞介素-3诱导MDS细胞中正常的STAT5反应，此外，在MDS中存在CD71(+) BM细胞亚群，其表型与正常骨髓中Epo反应细胞相似，我们得出结论，MDS中的Epo反应在Epo受体（EpoR）信号转导通路的早期点受到干扰。(C) 1997年由美国血液病学会出版。
Patients with myelodysplastic syndrome (MDS) have ineffective in vivo and in vitro erythropoiesis, characterized by an impaired response to erythropoietin (Epo). We examined proliferation and maturation of MDS marrow cells in response to Epo in more detail. Epo-dependent DNA synthesis as well as induction of GATA-1 binding activity in marrow cells from 15 MDS cases were severely reduced as compared with normal bone marrow (NBM). Additionally, the appearance of morphologically identifiable erythroid cells was decreased in MDS cell cultures. These data indicate that both the Epo-dependent proliferation as well as the differentiation induction by Epo is suppressed. To study more upstream events of the Epo signal transduction route we investigated activation of the signal transducer and activator of transcription (STAT) 5. In all 15 MDS samples tested, STAT5 activation was absent or greatly suppressed in response to Epo, In contrast, interleukin-3 induced a normal STAT5 response in MDS cells, Further, in MDS the subset of CD71(+) BM cells that is phenotypically similar to Epo-responsive cells in normal marrow, was present, We conclude that the Epo response in MDS is disturbed at an early point in the Epo receptor (EpoR) signal transduction pathway. (C) 1997 by The American Society of Hematology.