Setbp1 promotes the self-renewal of murine myeloid progenitors via activation of Hoxa9 and Hoxa10.

ABSTRACT: Acquisition of self-renewal capability by myeloid progenitors to become leukemic stem cells during myeloid leukemia development is poorly understood. Here, we show that Setbp1 overexpression efficiently confers self-renewal capability to myeloid progenitors in vitro, causing their immortalization in the presence of stem cell factor and IL-3. Self-renewal after immortalization requires continuous Setbp1 expression. We also found that Hoxa9 and Hoxa10 mRNA are present at dramatically higher levels in Setbp1-immortalized cells compared with other immortalized cells, and are induced shortly after Setbp1 expression in primary myeloid progenitors. Suppression of either gene in Setbp1-immortalized cells drastically reduces their colony-forming capability. Interestingly, Setbp1 protein associates

SUBMITTER: Oakley K 

PROVIDER: S-EPMC3383018 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature