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Lentiviral transduction of Bcr\u2010Abl into either Ba\/F3 or CD34<jats:sup>+<\/jats:sup> hematopoietic stem\/progenitor cells potently increased levels of AURKA and AURKB in association with phosphorylation of AKT and stimulated their proliferation. Bcr\u2010Abl\u2010mediated expression of AURKA and AURKB were decreased in CD34<jats:sup>+<\/jats:sup> HSPCs when AKT was inactivated by an shRNA against AKT, suggesting that Bcr\u2010Abl induced expression of AURKA and AURKB <jats:italic>via<\/jats:italic> AKT signaling. MLN8237, an inhibitor of AURKA, significantly inhibited the proliferation of freshly isolated CD34<jats:sup>+<\/jats:sup> CML cells in a dose\u2010dependent manner as measured by colony forming assay. Importantly, inhibition of AURKA in CD34<jats:sup>+<\/jats:sup> leukemia cells freshly isolated from individuals with blast crisis of CML with Bcr\u2010Abl T315I mutant (<jats:italic>n<\/jats:italic> = 2) by MLN8237 significantly impaired the engraftment of these cells in severely immunocompromised mice and decreased the weight of spleens. Taken together, Bcr\u2010Abl induces expression of AURKA and AURKB at least in part <jats:italic>via<\/jats:italic> AKT. Inhibition of AURKA could be useful to overcome imatinib\u2010resistance mediated by <jats:italic>Bcr\u2010Abl<\/jats:italic> mutants.<\/jats:p>","DOI":"10.1002\/ijc.28434","type":"journal-article","created":{"date-parts":[[2013,8,12]],"date-time":"2013-08-12T05:49:16Z","timestamp":1376286556000},"page":"1183-1194","source":"Crossref","is-referenced-by-count":36,"title":["Bcr\u2010Abl activates AURKA and AURKB in chronic myeloid leukemia cells <i>via<\/i> AKT signaling"],"prefix":"10.1002","volume":"134","author":[{"given":"Jing","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Hematology and Respiratory Medicine Kochi University Nankoku Kochi Japan"},{"name":"Department of Immunology Kochi Medical School, Kochi University, Kochi University Nankoku Kochi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Ikezoe","sequence":"additional","affiliation":[{"name":"Department of Hematology and Respiratory Medicine Kochi 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