The Importance of Mutational Analysis in Chronic Myeloid Leukaemia for Treatment Choice

Abstract

Since their introduction in 2001, tyrosine kinase inhibitors (TKIs) targeting BCR-ABL have become the standard therapy for chronic myeloid leukaemia (CML). While allogeneic hematopoietic stem cell transplant is a recognised curative treatment for CML, TKIs prevent progression to advanced phase in most patients, and spectacularly improve the disease burden (in deep molecular responders) and the overall survival of CML patients. However, mutations in the BCR-ABL kinase domain affect a significant proportion of CML patients and have been associated with primary or secondary (refractory disease following an initial response) resistance to imatinib. Such resistance may emerge at any time during TKI therapy and are a major mechanism of treatment failure, in addition to BCR-ABL1-independent treatment resistance and treatment intolerance mechanisms. In the context of the above-described clinical settings, the management of CML patients remains challenging. The detection of mutations following imatinib resistance is therefore crucial to ensure appropriate second or third-line drug selection.

Keywords

• chronic myeloid leukaemia (cml)
• bcr-abl
• ponatinib
• t315i
• mutational analysis
• tyrosine kinase inhibitors (tki)