Isoform-specific potentiation of stem and progenitor cell engraftment by AML1/RUNX1.

ABSTRACT:

Background

AML1/RUNX1 is the most frequently mutated gene in leukaemia and is central to the normal biology of hematopoietic stem and progenitor cells. However, the role of different AML1 isoforms within these primitive compartments is unclear. Here we investigate whether altering relative expression of AML1 isoforms impacts the balance between cell self-renewal and differentiation in vitro and in vivo.

Methods and findings

The human AML1a isoform encodes a truncated molecule with DNA-binding but no transactivation capacity. We used a retrovirus-based approach to transduce AML1a into primitive haematopoietic cells isolated from the mouse. We observed that enforced AML1a expression increased the competitive engraftment potential of murine long-term reconstituting stem cells w

SUBMITTER: Tsuzuki S 

PROVIDER: S-EPMC1868041 | biostudies-literature | 2007 May

REPOSITORIES: biostudies-literature