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.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Bresnick EH,Katsumura KR,Lee HY,Johnson KD,Perkins AS

doi

10.1093/nar/gks281

subject

Has Abstract

pub_date

2012-07-01 00:00:00

pages

5819-31

issue

13

eissn

0305-1048

issn

1362-4962

pii

gks281

journal_volume

40

pub_type

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