Collins C T, Hess J L
Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
Department of Pathology and Laboratory Medicine and Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Oncogene. 2016 Mar 3;35(9):1090-8. doi: 10.1038/onc.2015.174. Epub 2015 Jun 1.
HOXA9 is a homeodomain-containing transcription factor that has 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 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 greater than 50% of AML with overexpression of HOXA9.
HOXA9是一种含同源结构域的转录因子，在造血干细胞扩增中起重要作用，且在急性白血病中通常失调。急性髓系白血病中的多种上游基因改变导致HOXA9过表达，这是预后不良的有力预测指标。在许多情况下，HOXA9已被证明是维持白血病转化所必需的；然而，其促进白血病发生的分子机制仍不清楚。最近的研究表明，HOXA9通过与一组细胞特异性辅助因子和协同蛋白结合，在启动子远端增强子处调控下游基因表达。人们正在加大力度，以确定HOXA9过表达白血病中维持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过表达急性髓系白血病的新型疗法有大量机会。
