RUNX1/AML1: A Central Player in Hematopoiesis

Abstract

It has been well established that a number of transcription factors play critical roles in regulating the fate of hematopoietic stem cell populations. One of them is the leukemia-associated transcription factor acute myeloid leukemia 1 (AML1; also known as runt-related transcription factor 1, or RUNX1). This gene was originally cloned from the breakpoint of the t(8;21) reciprocal chromosome translocation and was later recognized as one of the most frequent targets of leukemia-associated gene aberrations. Gene-targeting experiments revealed that transcriptionally active AML1 is essential for the establishment of definitive hematopoiesis. More specifically, this gene functions in the emergence of the hematopoietic progenitor cells from the hemogenic endothelium by budding in the aorta-gonad-mesonephros region, and its expression points to the sites with strong potential for the emergence of hematopoietic stem cells. This review discusses aspects of the biologic properties of AML1 in early hematopoietic development.

The Bone-specific Expression of Runx2 Oscillates during the Cell Cycle to Support a G1-related Antiproliferative Function in Osteoblasts

“…Runx1 is a frequent target of chromosomal translocations in acute myelogenous leukemia (60,61), and Runx3 is associated with gastrointestinal hyperplasias and stomach cancer (62,63). Thus, it has now become apparent that the entire class of Runx-related transcription factors, which encompasses Runx1/AML1, Runx2/Cbfa1 and Runx3/ PEBP2␣C, regulates cell growth in a tissue-and cell typerestricted manner (23,31,60,(63)(64)(65)(66)(67).…”

The origin and fate of yolk sac hematopoiesis: application of chimera analyses to developmental studies

“…The obvious question of a potential lineage relationship between hemangioblasts and hemogenic endothelium is currently unclear. Very recently, a series of papers have proposed a model integrating both hemangioblast and hemogenic endothelium abnormalities in their vasculature, and die mainly of bleeding during fetal life (Okuda et al, 2001;Wang et al, 1996).…”

AML1/Runx1 Recruits Calcineurin to Regulate Granulocyte Macrophage Colony-stimulating Factor by Ets1 Activation

“…The Runx family of transcription factors plays important roles in development, and the three Runx proteins are also tumor suppressors (1)(2)(3)(4). Runx1, better known as acute myeloid leukemia 1 (AML1), 1 is essential for definitive hematopoiesis.…”

“…Runx1, better known as acute myeloid leukemia 1 (AML1), 1 is essential for definitive hematopoiesis. Genetic ablation of AML1 leads to a complete lack of fetal liver hematopoiesis, and AML1 is important at several levels of development of hematopoietic cells and regulation of the immune system (1,2). The AML1 gene is the most common target for chromosomal translocations in human leukemia (5).…”

“…The free RHD exists in a conformation in which affinity for DNA is nonoptimal, and CBF␤ binding to the RHD triggers a switch in the RHD structure that stabilizes it in a conformation for sustained DNA binding (13). CBF␤ is essential for Runx protein function because a homozygous mutation of CBF␤ results in a complete lack of fetal liver hematopoiesis (1,2) and severely defective bone formation (14,15).…”