BCR/ABL kinase induces self-mutagenesis via reactive oxygen species to encode imatinib resistance
作者： Mateusz Koptyra , Rafal Falinski , Michal O Nowicki , Tomasz Stoklosa , Ireneusz Majsterek
DOI: 10.1182/BLOOD-2005-07-2815
关键词:
摘要: Mutations in the BCR/ABL kinase domain play a major role in resistance to imatinib mesylate (IM). We report here that BCR/ABL kinase stimulates reactive oxygen species (ROS), which causes oxidative DNA damage, resulting in mutations in the kinase domain. The majority of mutations involved A/T→ G/C and G/C→ A/T transitions, a phenotype detected previously in patients, which encoded clinically relevant amino acid substitutions, causing IM resistance. This effect was reduced in cells expressing BCR/ABL (Y177F) …
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