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  • Title: Influence of enzyme and transporter polymorphisms on trough imatinib concentration and clinical response in chronic myeloid leukemia patients.
    Author: Seong SJ, Lim M, Sohn SK, Moon JH, Oh SJ, Kim BS, Ryoo HM, Chung JS, Joo YD, Bang SM, Jung CW, Kim DH, Park SY, Yoon SS, Kim I, Lee HG, Won JH, Min YH, Cheong JW, Park JS, Eom KS, Hyun MS, Kim MK, Kim H, Park MR, Park J, Kim CS, Kim HJ, Kim YK, Park EK, Zang DY, Jo DY, Lee HW, Yoon YR.
    Journal: Ann Oncol; 2013 Mar; 24(3):756-60. PubMed ID: 23117072.
    Abstract:
    BACKGROUND: This study explored the impact of genetic polymorphisms in cytochrome P450 (CYP) enzymes and transporters on the plasma trough concentration of imatinib mesylate (IM) and clinical response in chronic myeloid leukemia (CML). PATIENTS AND METHODS: In total, 82 patients with CML who had been administered 400 mg IM daily for over 6 months were genotyped for 11 single-nucleotide polymorphisms in nine genes (CYP3A4, CYP3A5, CYP2C9, CYP2C19, CYP2D6, ABCB1, SLC22A1, SLC22A2 and ABCG2) using blood samples. The trough imatinib concentration and clinical responses were assessed 6 months after the initiation of IM therapy. RESULTS: The CC, CA and AA genotypes in ABCG2 421C>A gave significantly different frequencies for the major molecular response (MMR) (P = 0.02). However, no significant differences were found between the genotypes of the CYP enzymes and transporters identified in this study and the imatinib plasma trough concentrations and clinical response frequencies, except for the correlation of ABCG2 with MMR. CONCLUSIONS: The results of the present study may indicate that the ABCG 421C>A genetic polymorphism influences the MMR of imatinib in patients with CML.
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