Musashi 2 regulates normal hematopoiesis and accelerates leukemogenesis (LSK and LK)

ABSTRACT: We demonstrate that Msi2 is the predominant form expressed in hematopoietic stem cells (HSC), and its knockdown leads to reduced engraftment and depletion of HSCs in vivo. Overexpression of Msi2 in a mouse model increases HSC cell cycle progression and cooperates with BCR-ABL1 to induce an aggressive leukemia. MSI2 is over-expressed in human myeloid leukemia, and expression levels directly correlate with decreased patient survival, thereby defining MSI2 expression as a novel prognostic marker in acute myeloid leukemia (AML). Depletion of MSI2 in human myeloid leukemia cells leads to decreased proliferation and apoptosis. These data implicate the MSI2 RNA binding protein in myeloid leukemogenesis and identify a novel potential target for therapy in AML. Mouse hematopoietic stem cells (defined as LineageLow, Sca1+, Kit+; LSK; n=3) as well as committed progenitor cells (LineageLow, Sca1-, Kit+; LK; n=3) were sorted and RNA was extracted using Qiagen RNeasy Micro Kit according to manufacturers instruction. cDNA was fragmented and biotinylated before hybridization onto Affymetrix Mouse Expression Array 430 2.0.

ORGANISM(S): Mus musculus

SUBMITTER: Fatima Al-Shahrour 

PROVIDER: E-GEOD-22774 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress