Article
BCR/ABL kinase induces self-mutagenesis via reactive oxygen species to encode imatinib resistance.
Blood - 1 Jul 2006
Koptyra Mateusz, Falinski Rafal, Nowicki Michal O, Stoklosa Tomasz, Majsterek Ireneusz, Nieborowska-Skorska Margaret, Blasiak Janusz, Skorski Tomasz
Abstract excerpt
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...
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