title: Master regulatory GATA transcription factors: mechanistic principles and emerging links to hematologic malignancies.
abstract: 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.
authors.affiliation: 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. ehbresni@wisc.edu
authors.forename: Emery H
authors.initials: EH
authors.lastname: Bresnick
authors.forename: Koichi R
authors.initials: KR
authors.lastname: Katsumura
authors.forename: Hsiang-Ying
authors.initials: HY
authors.lastname: Lee
authors.forename: Kirby D
authors.initials: KD
authors.lastname: Johnson
authors.forename: Archibald S
authors.initials: AS
authors.lastname: Perkins
mesh_terms: D050980:GATA Transcription Factors / Q000378:metabolism*; D050989:GATA2 Transcription Factor / Q000378:metabolism; D019337:Hematologic Neoplasms / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D011499:Protein Processing, Post-Translational
chemical_list: D050980:GATA Transcription Factors; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human