In Vivo RNA Interference Screening Identifies a Leukemia-Specific Dependence on Integrin Beta 3 Signaling

ABSTRACT: Primary leukemia stem cells (LSCs) reside in an in vivo microenvironment that supports the growth and survival of malignant cells. We used an in vivo short hairpin RNA (shRNA) screening approach to identify novel genes that are essential for primary murine MLL-AF9 acute myeloid leukemia (AML). We found that Integrin Beta 3 (Itgb3) is selectively essential for murine leukemia cells in vivo, and for human leukemia cells in xenotransplantation studies. In leukemia cells, Itgb3 knockdown impaired homing, downregulated LSC transcriptional programs, and induced differentiation. In contrast, loss of Itgb3 in normal HSPCs did not affect engraftment, reconstitution, or differentiation in long term transplantation assays. We explored the signaling pathways downstream of Itgb3 using an additional in

ORGANISM(S): Mus musculus

SUBMITTER: Fatima Al-Shahrour 

PROVIDER: E-GEOD-46307 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress