, Volume 84, Issue 2, pp 136-142

AML1/Runx1 as a Versatile Regulator of Hematopoiesis: Regulation of Its Function and a Role in Adult Hematopoiesis

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Abstract

AML1/Runx1, originally identified as a gene located at the breakpoint of the t(8;21) translocation, encodes a transcription factor that is widely expressed in multiple hematopoietic lineages and that regulates the expression of a variety of hemato-poietic genes. Numerous studies have shown that AML1 is a critical regulator of hematopoietic development. In addition, AML1 is a frequent target for chromosomal translocation in human leukemia.The activity of AML1 can be modulated by various types of posttranslational modification, including phosphorylation and acetylation. Phosphorylation by extracellular signal-regulated kinase (ERK) is one of the mechanisms that dictate whether AML1 acts as either a transcriptional repressor or an activator of gene expression. Recently, a physiological role for AML1 in adult hematopoiesis was revealed by conditional gene targeting in mice. Remarkably, adult hematopoietic progenitors are maintained even in the absence of AML1, in stark contrast to the total disruption of definitive hematopoiesis during embryogenesis. AML1 is, however, critical for megakaryopoiesis and plays an important role in T-cell and B-cell development in adult mice. Recent analyses engineered to recreate hematopoiesis in vitro revealed that the transcriptional activity of AML1 is closely related with the potential of AML1 to generate hematopoietic cells and support thymocyte development.