Heterogeneous nuclear ribonucleoprotein K is overexpressed in acute myeloid leukemia and causes myeloproliferation in mice via altered Runx1 splicing.
Heterogeneous nuclear ribonucleoprotein K is overexpressed in acute myeloid leukemia and causes myeloproliferation in mice via altered Runx1 splicing.
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作者：
急性髓性白血病（AML）是由许多促进疾病进展的分子事件驱动的。在此，我们确定hnRNP K过表达是AML中一种复发性异常，与患者生存率呈负相关。hnRNP K在小鼠胎儿肝细胞中的过度表达导致自我更新和分化潜能的改变。此外，小鼠移植模型显示，hnRNP K过表达导致体内骨髓增生。机制研究揭示了hnRNP K和runx1之间的直接功能关系，runx1是造血功能的主要转录调节因子，在白血病中经常失调。分子分析表明，hnRNP K的过表达导致RUNX1缺乏外显子4的选择性剪接异构体的富集。我们的工作确定了hnRNP K通过调控RUNX1剪接和随后的转录活性来影响骨髓发生的致癌潜力。
Acute myeloid leukemia (AML) is driven by numerous molecular events that contribute to disease progression. Herein, we identify hnRNP K overexpression as a recurrent abnormality in AML that negatively correlates with patient survival. Overexpression of hnRNP K in murine fetal liver cells results in altered self-renewal and differentiation potential. Further, murine transplantation models reveal that hnRNP K overexpression results in myeloproliferation in vivo. Mechanistic studies expose a direct functional relationship between hnRNP K and RUNX1—a master transcriptional regulator of hematopoiesis often dysregulated in leukemia. Molecular analyses show that overexpression of hnRNP K results in an enrichment of an alternatively spliced isoform of RUNX1 lacking exon 4. Our work establishes hnRNP K’s oncogenic potential in influencing myelogenesis through its regulation of RUNX1 splicing and subsequent transcriptional activity.
影响因子：
2.6
作者：
Padovani KS;Goto RN;Fugio LB;Garcia CB;Alves VM;Brassesco MS;Greene LJ;Rego EM;Leopoldino AM
通讯作者：
Leopoldino AM