Mutation in the ABL kinase domain is the principal mechanism of imatinib resistance. MK-0457 is a small molecule inhibitor of the Aurora kinase family, but the mechanism of MK-0457 has not been evaluated, In this study, the gene expression profiles and intracellular signaling of chronic myeloid leukemia (CML) cell line K562 exposed to imatinib or MK-0457. MK-0457 induced cell growth inhibition in K562 cells. In gene expression profiles, there was an increase of 938 genes in imatinib and 895 genes in MK-0457 and 638 genes overlapped. In contrast, there was a decrease of 597 genes in imatinib and 582 genes in MK0457 and 406 genes overlapped. These down-regulated genes include heat shock proteins (HSPs). These results indicate that MK-0457 is effective in CM cells by the down-regulation of HSPs which may relate to BCR ABL stability, and offer new information regarding the molecular basis of strategy against to CML. Crown Copyright (C) 2009 Published by Elsevier Inc. All rights reserved.