Gene expression signatures associated with the in vitro resistance to two tyrosine kinase inhibitors, nilotinib and imatinib.

ABSTRACT: The use of selective inhibitors targeting Bcr-Abl kinase is now established as a standard protocol in the treatment of chronic myelogenous leukemia; however, the acquisition of drug resistance is a major obstacle limiting the treatment efficacy. To elucidate the molecular mechanism of drug resistance, we established K562 cell line models resistant to nilotinib and imatinib. Microarray-based transcriptome profiling of resistant cells revealed that nilotinib- and imatinib-resistant cells showed the upregulation of kinase-encoding genes (AURKC, FYN, SYK, BTK and YES1). Among them, the upregulation of AURKC and FYN was observed both in nilotinib- and imatinib-resistant cells irrespective of exposure doses, while SYK, BTK and YES1 showed dose-dependent upregulation of expression. Upregulation o

SUBMITTER: Kim TM 

PROVIDER: S-EPMC3255246 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature