Stat3 promotes the development of erythroleukemia by inducing Pu.1 expression and inhibiting erythroid differentiation.
Stat3 promotes the development of erythroleukemia by inducing Pu.1 expression and inhibiting erythroid differentiation.
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STAT3通过诱导PU.1表达并抑制红细胞分化来促进红血病的发展。
DOI：
10.1038/onc.2009.202
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发表时间：
2009-09-24
期刊：
影响因子：
8
通讯作者：
Hankey, P. A.
中科院分区：
文献类型：
--
作者：
Hegde, S.;Ni, S.;He, S.;Yoon, D.;Feng, G. S.;Watowich, S. S.;Paulson, R. F.;Hankey, P. A.
白血病发生需要两类突变，一类促进增殖，另一类阻断分化。由Friend病毒诱导的红白血病是一种多阶段疾病，其特征在于由病毒糖蛋白gp 55与Sf-Stk和EpoR的相互作用驱动的早期增殖阶段，以及由逆转录病毒插入Pu.1基因座导致的晚期分化阻断。我们在这里证明，在疾病的早期阶段由Sf-Stk激活Stat 3对于在由EpoR诱导的分化信号的存在下的红白血病的进展是必不可少的，但是在疾病的晚期阶段是不可缺少的。此外，我们确定Pu.1作为Stat 3靶基因在红白血病发展的早期阶段。我们的研究结果支持了一种模型，即在疾病的早期阶段，Stat 3的激活通过上调Pu.1在调节分化中起着关键作用，从而抑制分化，有利于感染的成红细胞的扩增，并增强可用于获得额外突变的祖细胞库，包括Pu.1的插入激活，导致完全白血病转化。
Leukemogenesis requires two classes of mutations, one that promotes proliferation and one that blocks differentiation. The erythroleukemia induced by Friend virus is a multistage disease characterized by an early proliferative stage driven by the interaction of the viral glycoprotein, gp55, with Sf-Stk and the EpoR, and a late block to differentiation resulting from retroviral insertion in the Pu.1 locus. We demonstrate here that activation of Stat3 by Sf-Stk in the early stage of disease is essential for the progression of erythroleukemia in the presence of differentiation signals induced by the EpoR, but is dispensable in the late stages of the disease. Furthermore, we identify Pu.1 as a Stat3 target gene in the early stages of erythroleukemia development. Our results support a model whereby the activation of Stat3 in the early stage of disease plays a pivotal role in regulating differentiation through the upregulation of Pu.1, thus inhibiting differentiation and favoring the expansion of infected erythroblasts and enhancing the pool of progenitors available for the acquisition of additional mutations, including insertional activation of Pu.1, resulting in full leukemic transformation.
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