Mechanisms of resistance to BCR–ABL kinase inhibitors

Abstract

Since the introduction of imatinib mesylate (IM) for the treatment of chronic myeloid leukemia (CML), impressive clinical responses have been observed in the majority of patients in chronic phase. However, not all patients experience an optimal response to IM or even to the more potent, second-generation tyrosine kinase inhibitors (TKIs). Furthermore, responses are not sustained in a number of patients, and it is yet unclear whether the inhibitors can be safely discontinued in patients who achieve long-term remission. The emergence of resistance to TKIs has become a significant problem that has led to extensive studies on the causal mechanisms. This review describes our current state of knowledge on why and how CML cells can develop resistance to TKIs.

Keywords:

• TKI
• CML
• BCR–ABL

Acknowledgements

We are grateful to Susan Branford for help with the literature review and ideas for figures.

Declaration of interest: J.V.M. is grateful for grant support from SA Pathology (Australia) and the National Institute for Health Research (NIHR) Biomedical Research Centre (UK) funding scheme.