The Impact of CYP۲D۶ Gene Polymorphisms on the Metabolism and Efficacy of Imatinib in Patients with Chronic Myeloid Leukemia (CML)

Chronic Myeloid Leukemia (CML) is a type of cancer that affects the bone marrow and blood. Imatinib is a targeted therapy commonly used to treat CML by inhibiting the BCR-ABL tyrosine kinase. However, individual responses to Imatinib vary significantly among patients. One potential factor influencing this variability is the genetic polymorphism in the CYP۲D۶ gene, which plays a crucial role in drug metabolism. This study aims to investigate the impact of CYP۲D۶ polymorphisms on the metabolism and therapeutic efficacy of Imatinib in CML patients. Material and Methods: A total of ۱۵۰ CML patients receiving Imatinib treatment were enrolled in this study, consisting of ۸۵ males and ۶۵ females. The mean age of the sample population was ۵۲.۳ years. Genotyping for CYP۲D۶ polymorphisms was performed using PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism) analysis. The metabolic activity of Imatinib was assessed by measuring plasma drug concentrations, and therapeutic efficacy was evaluated based on hematologic and cytogenetic response criteria over a ۱۲-month follow-up period. Results: Out of the ۱۵۰ patients, ۴۵ (۳۰%) exhibited poor metabolizer (PM) genotype, ۷۵ (۵۰%) had an intermediate metabolizer (IM) genotype, and ۳۰ (۲۰%) were classified as extensive metabolizers (EM). The average plasma concentration of Imatinib was significantly higher in PM patients (۳۴۵۰ ng/mL) compared to IM (۲۶۰۰ ng/mL) and EM patients (۱۵۰۰ ng/mL). Hematologic response rates were ۶۰% in PM, ۷۵% in IM, and ۹۰% in EM patients. Cytogenetic response rates were observed at ۵۰% in PM, ۷۰% in IM, and ۸۵% in EM patients. Conclusion: CYP۲D۶ polymorphisms significantly influence the metabolism and efficacy of Imatinib in CML patients. Poor metabolizers exhibit higher plasma concentrations of the drug but have lower hematologic and cytogenetic response rates compared to intermediate and extensive metabolizers. These findings suggest that genotyping for CYP۲D۶ polymorphisms may be valuable in personalizing Imatinib therapy for improved clinical outcomes in CML patients.

کلیدواژه ها:

Chronic Myeloid Leukemia ، Imatinib ، CYP۲D۶ Polymorphisms ، Drug Metabolism ، Personalized Medicine