Mechanism of MK-0457 efficacy against BCR-ABL positive leukemia cells

作者：Okabe Seiichi^*; Tauchi Tetsuzo; Ohyashiki Junko H; Ohyashiki Kazuma

来源：Biochemical and Biophysical Research Communications, 2009, 380(4): 775-779.

DOI：10.1016/j.bbrc.2009.01.141

• Chronic myeloid leukemia
• MK 0457
• Imatinib
• Heat shock protein

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.

• 出版日期2009-3-20