Mutation in Abl kinase with altered drug-binding kinetics indicates a novel mechanism of imatinib resistance.

ABSTRACT: Protein kinase inhibitors are potent anticancer therapeutics. For example, the Bcr-Abl kinase inhibitor imatinib decreases mortality for chronic myeloid leukemia by 80%, but 22 to 41% of patients acquire resistance to imatinib. About 70% of relapsed patients harbor mutations in the Bcr-Abl kinase domain, where more than a hundred different mutations have been identified. Some mutations are located near the imatinib-binding site and cause resistance through altered interactions with the drug. However, many resistance mutations are located far from the drug-binding site, and it remains unclear how these mutations confer resistance. Additionally, earlier studies on small sets of patient-derived imatinib resistance mutations indicated that some of these mutant proteins were in fact sensitive t

SUBMITTER: Lyczek A 

PROVIDER: S-EPMC8609647 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature