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

dc.contributor.authorMiller, Peter G.
dc.contributor.authorAl-Shahrour, Fatima
dc.contributor.authorHartwell, Kimberly A.
dc.contributor.authorChu, Lisa P.
dc.contributor.authorJaras, Marcus
dc.contributor.authorPuram, Rishi V.
dc.contributor.authorPuissant, Alexandre
dc.contributor.authorCallahan, Kevin P.
dc.contributor.authorAshton, John
dc.contributor.authorMcConkey, Marie
dc.contributor.authorPoveromo, Luke P.
dc.contributor.authorCowley, Glenn S.
dc.contributor.authorKharas, Michael G.
dc.contributor.authorLabelle, Myriam
dc.contributor.authorShterental, Sebastian
dc.contributor.authorFujisaki, Joji
dc.contributor.authorSilberstein, Lev
dc.contributor.authorAlexe, Gabriela
dc.contributor.authorAl-Hajj, Muhammad A.
dc.contributor.authorShelton, Christopher A.
dc.contributor.authorArmstrong, Scott A.
dc.contributor.authorRoot, David E.
dc.contributor.authorScadden, David T.
dc.contributor.authorMukherjee, Siddhartha
dc.contributor.authorStegmaier, Kimberly
dc.contributor.authorJordan, Craig T.
dc.contributor.authorEbert, Benjamin L.
dc.contributor.authorHynes, Richard O
dc.date.accessioned2015-04-08T18:29:38Z
dc.date.available2015-04-08T18:29:38Z
dc.date.issued2013-06
dc.date.submitted2013-02
dc.identifier.issn15356108
dc.identifier.urihttp://hdl.handle.net/1721.1/96466
dc.description.abstractWe 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.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Harvard Stem Cell Institute. GlaxoSmithKline. Grant P01 CA108631)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Harvard Stem Cell Institute. GlaxoSmithKline. Grant RC1 CA145229)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Harvard Stem Cell Institute. GlaxoSmithKline. Grant R01 CA140292)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Harvard Stem Cell Institute. GlaxoSmithKline. Grant CA148180)en_US
dc.language.isoen_US
dc.publisherElsevieren_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.ccr.2013.05.004en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourceElsevier Open Archiveen_US
dc.titleIn Vivo RNAi Screening Identifies a Leukemia-Specific Dependence on Integrin Beta 3 Signalingen_US
dc.typeArticleen_US
dc.identifier.citationMiller, Peter G., Fatima Al-Shahrour, Kimberly A. Hartwell, Lisa P. Chu, Marcus Jaras, Rishi V. Puram, Alexandre Puissant, et al. “In Vivo RNAi Screening Identifies a Leukemia-Specific Dependence on Integrin Beta 3 Signaling.” Cancer Cell 24, no. 1 (July 2013): 45–58. © 2013 Elsevier Inc.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentKoch Institute for Integrative Cancer Research at MITen_US
dc.contributor.mitauthorHynes, Richard O.en_US
dc.contributor.mitauthorLabelle, Myriamen_US
dc.relation.journalCancer Cellen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsMiller, Peter G.; Al-Shahrour, Fatima; Hartwell, Kimberly A.; Chu, Lisa P.; Jaras, Marcus; Puram, Rishi V.; Puissant, Alexandre; Callahan, Kevin P.; Ashton, John; McConkey, Marie E.; Poveromo, Luke P.; Cowley, Glenn S.; Kharas, Michael G.; Labelle, Myriam; Shterental, Sebastian; Fujisaki, Joji; Silberstein, Lev; Alexe, Gabriela; Al-Hajj, Muhammad A.; Shelton, Christopher A.; Armstrong, Scott A.; Root, David E.; Scadden, David T.; Hynes, Richard O.; Mukherjee, Siddhartha; Stegmaier, Kimberly; Jordan, Craig T.; Ebert, Benjamin L.en_US
dc.identifier.orcidhttps://orcid.org/0000-0001-7603-8396
mit.licensePUBLISHER_POLICYen_US
mit.metadata.statusComplete


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