hnRNP K Is a Haploinsufficient Tumor Suppressor that Regulates Proliferation and Differentiation Programs in Hematologic Malignancies.
hnRNP K Is a Haploinsufficient Tumor Suppressor that Regulates Proliferation and Differentiation Programs in Hematologic Malignancies.
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DOI：
10.1016/j.ccell.2015.09.001
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发表时间：
2015-10-12
期刊：
影响因子：
50.3
通讯作者：
Post SM
中科院分区：
文献类型：
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作者：
Gallardo M;Lee HJ;Zhang X;Bueso-Ramos C;Pageon LR;McArthur M;Multani A;Nazha A;Manshouri T;Parker-Thornburg J;Rapado I;Quintas-Cardama A;Kornblau SM;Martinez-Lopez J;Post SM
hnRNP K调节细胞程序，其表达和突变状态的变化与恶性肿瘤有关。为了直接检查其在肿瘤发生中的作用，我们产生了携带Hnrnpk敲除等位基因（Hnrnpk+/−）的小鼠模型。Hnrnpk单倍不足导致生存率降低，肿瘤形成增加，基因组不稳定，以及可移植造血肿瘤伴骨髓增生的发生。减少hnRNP K表达减弱p21激活，下调C/EBP水平，并激活STAT 3信号。此外，对9号染色体部分缺失的原发性急性髓性白血病患者的样本分析显示HNRNPK表达显著降低。总之，这些数据暗示hnRNP K在血液系统疾病的发展，并建议hnRNP K作为一种肿瘤抑制剂。
hnRNP K regulates cellular programs and changes in its expression and mutational status have been implicated in neoplastic malignancies. To directly examine its role in tumorigenesis, we generated a mouse model harboring an Hnrnpk knock-out allele (Hnrnpk+/−). Hnrnpk haploinsufficiency resulted in reduced survival, increased tumor formation, genomic instability, and the development of transplantable hematopoietic neoplasms with myeloproliferation. Reduced hnRNP K expression attenuated p21 activation, downregulated C/EBP levels, and activated STAT3 signaling. Additionally, analysis of samples from primary acute myeloid leukemia patients harboring a partial deletion of chromosome 9 revealed a significant decrease in HNRNPK expression. Together, these data implicate hnRNP K in the development of hematological disorders and suggest hnRNP K acts as a tumor suppressor.