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Despite the great efficacy of the Bcr\u2010Abl\u2010specific inhibitor imatinib, resistance to this drug is recognized as a major problem in CML treatment. We found that in LAMA84 cells, characterized by imatinib\u2010resistance caused by BCR\u2010ABL1 gene amplification, the pro\u2010survival protein kinase CK2 is up\u2010regulated as compared to the sensitive cells. CK2 exhibits a higher protein\u2010level and a parallel enhancement of catalytic activity. Consistently, CK2\u2010catalysed phosphorylation of Akt\u2010Ser129 is increased. CK2 co\u2010localizes with Bcr\u2010Abl in the cytoplasmic fraction as judged by subcellular fractionation and fluorescence immunolocalization. CK2 and Bcr\u2010Abl are members of the same multi\u2010protein complex(es) in imatinib\u2010resistant cells as demonstrated by co\u2010immunoprecipitation and co\u2010sedimentation in glycerol gradients. Cell treatment with CX\u20104945, a CK2 inhibitor currently in clinical trials, counteracts CK2\/Bcr\u2010Abl interaction and causes cell death by apoptosis. Interestingly, combination of CX\u20104945 with imatinib displays a synergistic effect in reducing cell viability. Consistently, knockdown of CK2\u03b1 expression by siRNA restores the sensitivity of resistant LAMA84 cells to low imatinib concentrations. Remarkably, the CK2\/Bcr\u2010Abl interaction and the sensitization towards imatinib obtained by CK2\u2010inhibition in LAMA84 is observable also in other imatinib\u2010resistant CML cell lines.<\/jats:p><jats:p>These results demonstrate that CK2 contributes to strengthen the imatinib\u2010resistance phenotype of CML cells conferring survival advantage against imatinib. We suggest that CK2 inhibition might be a promising tool for combined strategies in CML therapy.<\/jats:p>","DOI":"10.1016\/j.molonc.2013.08.006","type":"journal-article","created":{"date-parts":[[2013,8,22]],"date-time":"2013-08-22T06:15:15Z","timestamp":1377152115000},"page":"1103-1115","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Aberrant signalling by protein kinase CK2 in imatinib\u2010resistant chronic myeloid leukaemia cells: Biochemical evidence and therapeutic 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