Wisconsin Institutes for Medical Research, Paul Carbone Cancer Center, Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA.
Nucleic Acids Res. 2012 Jul;40(13):5819-31. doi: 10.1093/nar/gks281. Epub 2012 Apr 5.
Numerous examples exist of how disrupting the actions of physiological regulators of blood cell development yields hematologic malignancies. The master regulator of hematopoietic stem/progenitor cells GATA-2 was cloned almost 20 years ago, and elegant genetic analyses demonstrated its essential function to promote hematopoiesis. While certain GATA-2 target genes are implicated in leukemogenesis, only recently have definitive insights emerged linking GATA-2 to human hematologic pathophysiologies. These pathophysiologies include myelodysplastic syndrome, acute myeloid leukemia and an immunodeficiency syndrome with complex phenotypes including leukemia. As GATA-2 has a pivotal role in the etiology of human cancer, it is instructive to consider mechanisms underlying normal GATA factor function/regulation and how dissecting such mechanisms may reveal unique opportunities for thwarting GATA-2-dependent processes in a therapeutic context. This article highlights GATA factor mechanistic principles, with a heavy emphasis on GATA-1 and GATA-2 functions in the hematopoietic system, and new links between GATA-2 dysregulation and human pathophysiologies.
有许多例子表明，干扰血细胞发育的生理调节剂的作用会导致血液系统恶性肿瘤。造血干细胞/祖细胞的主调控因子 GATA-2 近 20 年前被克隆，精致的遗传分析证明了它促进造血的基本功能。虽然某些 GATA-2 靶基因与白血病的发生有关，但直到最近才明确发现 GATA-2 与人类血液病理生理学有关。这些病理生理学包括骨髓增生异常综合征、急性髓系白血病和一种免疫缺陷综合征，其表型复杂，包括白血病。由于 GATA-2 在人类癌症的病因学中起着关键作用，因此考虑正常 GATA 因子功能/调节的机制以及如何剖析这些机制可能会为在治疗环境中阻止 GATA-2 依赖性过程提供独特的机会是有益的。本文重点介绍 GATA 因子的机制原理，重点介绍 GATA-1 和 GATA-2 在造血系统中的功能，以及 GATA-2 失调与人类病理生理学之间的新联系。
