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Nevertheless, resistance to imatinib emerges as CML progresses to an acute deadly phase implying that physiopathologically relevant cellular targets should be validated to develop alternative therapeutic strategies. The NF\u2010\u03baB transcription factor that exerts pro\u2010survival actions is found abnormally active in numerous hematologic malignancies. In the present study, using Bcr\u2010Abl\u2010transfected BaF murine cells, LAMA84 human CML cell line and primary CML, we show that NF\u2010\u03baB is active downstream of Bcr\u2010Abl. Pharmacological blockade of NF\u2010\u03baB by the IKK2 inhibitor AS602868 prevented survival of BaF cells expressing either wild\u2010type, M351T or T315I imatinib\u2010resistant mutant forms of Bcr\u2010Abl both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> using a mouse xenograft model. AS602868 also affected the survival of LAMA84 cells and of an imatinib\u2010resistant variant. Importantly, the IKK2 inhibitor strongly decreased <jats:italic>in vitro<\/jats:italic> survival and ability to form hematopoietic colonies of primary imatinib resistant CML cells including T315I cells. Our data strongly support the targeting of NF\u2010\u03baB as a promising new therapeutic opportunity for the treatment of imatinib resistant CML patients in particular in the case of T315I patients. The T315I mutation escapes all currently used Bcr\u2010Abl inhibitors and is likely to become a major clinical problem as it is associated with a poor clinical outcome. \u00a9 2009 UICC<\/jats:p>","DOI":"10.1002\/ijc.24294","type":"journal-article","created":{"date-parts":[[2009,1,22]],"date-time":"2009-01-22T20:10:26Z","timestamp":1232655026000},"page":"308-317","source":"Crossref","is-referenced-by-count":38,"title":["NF\u2010\u03baB inhibition triggers death of imatinib\u2010sensitive and imatinib\u2010resistant chronic myeloid leukemia cells including T315I Bcr\u2010Abl 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