Aim: Imatinib is a tyrosine kinase inhibitor that has revolutionized the treatment of chronic myeloid leukemia (CML). Despite its efficacy, about a third of patients discontinue the treatment due to therapy failure or intolerance. The rational identification of patients less likely to respond to imatinib would be of paramount clinical relevance. We have shown that transmembrane transporter hOCT1 genotyping predicts imatinib activity. In parallel, Polycomb group genes (PcGs) are epigenetic repressors implicated in CML progression and in therapy resistance.
Patients & methods: We measured the expression of eight PcGs in paired pre- and post-imatinib bone marrow samples from 30 CML patients.
Results: BMI1, PHC3, CBX6 and CBX7 expression was significantly increased during imatinib treatment. Post-treatment levels of CBX6 and CBX7 predicted 3-month response rate. Measurement of post-treatment BMI1 levels improved the predictive power of hOCT1 genotyping.
Conclusion: These results suggest that the expression levels of PcGs might be useful for a more accurate risk stratification of CML patients.
Keywords: BMI1; CBX6; CBX7; Polycomb; imatinib; pharmacoepigenetics.