Role of HOXA9 in leukemia: dysregulation, cofactors and essential targets.
Role of HOXA9 in leukemia: dysregulation, cofactors and essential targets.
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DOI：
10.1038/onc.2015.174
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发表时间：
2016-03-03
期刊：
影响因子：
8
通讯作者：
Hess JL
中科院分区：
文献类型：
--
作者：
Collins CT;Hess JL
HOXA9是一种含有同源结构域的转录因子，在造血干细胞扩增中发挥重要作用，在急性白血病中常被解除调控。急性髓系白血病(AML)的多种上游基因改变导致HOXA9的过度表达，这是预后不良的有力预测因素。在许多情况下，HOXA9被证明是维持白血病转化所必需的，然而它促进白血病发生的分子机制仍然不清楚。最近的工作已经证实，HOXA9通过与启动子远端增强子以及细胞特异性辅因子和协作者蛋白的子集结合来调节下游基因的表达。目前正在加紧努力，以确定维持HOXA9过度表达白血病转化所需的关键辅助因子和靶基因。随着对HOXA9介导的转化的理解不断深入，开发适用于超过50%的HOXA9过表达的AML的新疗法将有大量的机会。
HOXA9 is a homeodomain-containing transcription factor that plays an important role in hematopoietic stem cell expansion and is commonly deregulated in acute leukemias. A variety of upstream genetic alterations in acute myeloid leukemia (AML) lead to overexpression of HOXA9, which is a strong predictor of poor prognosis. In many cases, HOXA9 has been shown to be necessary for maintaining leukemic transformation, however the molecular mechanisms through which it promotes leukemogenesis remain elusive. Recent work has established that HOXA9 regulates downstream gene expression through binding at promoter distal enhancers along with a subset of cell-specific cofactor and collaborator proteins. Increasing efforts are being made to identify both the critical cofactors and target genes required for maintaining transformation in HOXA9-overexpressing leukemias. With continued advances in understanding HOXA9-mediated transformation, there is a wealth of opportunity for developing novel therapeutics that would be applicable for the greater than 50% of AML with overexpression of HOXA9.
影响因子：
2.5
作者：
Misra, Mala;Sours, Emily;Lance-Jones, Cynthia
通讯作者：
Lance-Jones, Cynthia