Unknown

Dataset Information

0

In Vivo RNAi screening identifies a leukemia-specific dependence on integrin beta 3 signaling.

ABSTRACT: We used an in vivo small hairpin RNA (shRNA) screening approach to identify genes that are essential for MLL-AF9 acute myeloid leukemia (AML). We found that Integrin Beta 3 (Itgb3) is 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 via the intracellular kinase Syk. In contrast, loss of Itgb3 in normal hematopoietic stem and progenitor cells did not affect engraftment, reconstitution, or differentiation. Finally, using an Itgb3 knockout mouse model, we confirmed that Itgb3 is dispensable for normal hematopoiesis but is required for leukemogenesis. Our results establish the significance of the Itgb3 signaling pathway as a potential therapeutic target in AML.

SUBMITTER: Miller PG 

PROVIDER: S-EPMC3746037 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

We used an in vivo small hairpin RNA (shRNA) screening approach to identify genes that are essential for MLL-AF9 acute myeloid leukemia (AML). We found that Integrin Beta 3 (Itgb3) is 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 via the intracellular kinase Syk. In contrast, loss of Itgb3 in normal hematopoietic st  ...[more]

Similar Datasets

Transcriptomics In Vivo RNA Interference Screening Identifies a Leukemia-Specific Dependence on Integrin Beta 3 Signaling
2013-04-24 | E-GEOD-46307 | biostudies-arrayexpress
Transcriptomics In Vivo RNA Interference Screening Identifies a Leukemia-Specific Dependence on Integrin Beta 3 Signaling
2013-04-24 | E-GEOD-46302 | biostudies-arrayexpress
Transcriptomics In Vivo RNA Interference Screening Identifies a Leukemia-Specific Dependence on Integrin Beta 3 Signaling
2013-04-24 | GSE46307 | GEO
Transcriptomics In Vivo RNA Interference Screening Identifies a Leukemia-Specific Dependence on Integrin Beta 3 Signaling
2013-04-24 | GSE46302 | GEO
Unknown RNAi screening of the tyrosine kinome identifies therapeutic targets in acute myeloid leukemia.
| S-EPMC2234058 | biostudies-literature
Unknown Comprehensive RNAi-based screening of human and mouse TLR pathways identifies species-specific preferences in signaling protein use.
| S-EPMC5381726 | biostudies-literature
Unknown In vivo RNAi screening identifies a mechanism of sorafenib resistance in liver cancer.
| S-EPMC4587571 | biostudies-literature
Unknown Genome-wide RNAi screening identifies host restriction factors critical for in vivo AAV transduction.
| S-EPMC4568673 | biostudies-literature
Unknown In vivo RNAi screening identifies regulators of actin dynamics as key determinants of lymphoma progression.
| S-EPMC2756700 | biostudies-literature
Unknown RNAi screening identifies mediators of NOD2 signaling: implications for spatial specificity of MDP recognition.
| S-EPMC3535590 | biostudies-literature