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|Title:||Mutational analysis in chronic myeloid leukemia: When and what to do?|
|Citation:||Current Opinion in Hematology, 2011; 18(2):111-116|
|Publisher:||Lippincott Williams & Wilkins|
|Susan Branford and Timothy P. Hughes|
|Abstract:||<h4>Purpose of review</h4>Imatinib, which was the first targeted therapy for patients with chronic myeloid leukemia (CML), has led to the significant prolongation of life for most patients. However, approximately 30% fail therapy. The major mechanism of acquired resistance is somatic mutation within the BCR-ABL1 kinase domain, which affects imatinib binding. Recently, more potent inhibitors have been approved that retain activity against most of the more than 100 mutations. However, some mutations remain problematic for one or more of the new inhibitors. The most frequently detected mutation, T315I, remains resistant to all of the currently approved inhibitors. More sensitive mutation techniques that focus on the detection of a limited number of specific mutations may be beneficial, but are yet to prove their clinical utility for the early detection of relapse in routine practice.<h4>Recent findings</h4>Inhibitors with alternate binding modes that may overcome T315I-associated resistance are at the preclinical stage or are undergoing clinical trial.<h4>Summary</h4>Each of the new, more potent kinase inhibitor drugs appear to have a partially overlapping set of mutations that confer a degree of resistance. Mutation detection techniques may need to adapt to provide clinicians with a more timely indication of mutation acquisition and pending relapse.|
|Keywords:||BCR-ABL1 kinase domain mutations; chronic myeloid leukemia; kinase inhibitor therapy|
|Rights:||© 2011 Lippincott Williams & Wilkins, Inc.|
|Appears in Collections:||Medicine publications|
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