Genetic mutations in chronic myelogenous leukemia: when to check and what to do?

PURPOSE OF REVIEW: The review will appraise the literature concerning ABL kinase domain mutations that has appeared over the last year and identify new questions, answers to old questions, and discuss new trends in clinical and laboratory based research.

RECENT FINDINGS: A concise summary of European LeukemiaNet guidelines for kinase domain mutation studies was published this year. A new controversial topic emerged: the relevance of IC50 data to guide second-line tyrosine kinase inhibitor (TKI) therapy. Although flaws in the methodology have been acknowledged, one group summarily rejected IC50 data and recommended that clinicians use individual patient comorbidities and drug safety profiles. The influence of kinase domain mutations on response to second-line and third-line TKI therapy was also published this year; unexpectedly, kinase domain mutations were found to have no effect on response or survival. However, the presence of a kinase domain mutation did influence survival following hematopoietic stem cell transplantation. Lastly, new findings from laboratories identified transcription factors BCL6 and STAT5 as potential new treatment targets.

SUMMARY: The last 12 months has brought much attention to clinical management of patients with kinase domain mutations and identified a new controversy concerning IC50 data use in the clinic. Kinase domain mutations do not appear to influence response to second-line and third-line response to TKI therapy. New targets that do not directly involve BCR-ABL added potential new therapeutic approaches.