title: Mechanism of MK-0457 efficacy against BCR-ABL positive leukemia cells.
abstract: 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 MK-0457 and 406 genes overlapped. These down-regulated genes include heat shock proteins (HSPs). These results indicate that MK-0457 is effective in CML 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.
authors.affiliation: First Department of Internal Medicine, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan. okabe@tokyo-med.ac.jp
authors.forename: Seiichi
authors.initials: S
authors.lastname: Okabe
authors.forename: Tetsuzo
authors.initials: T
authors.lastname: Tauchi
authors.forename: Junko H
authors.initials: JH
authors.lastname: Ohyashiki
authors.forename: Kazuma
authors.initials: K
authors.lastname: Ohyashiki