Annals of oncology : official journal of the European Society for Medical Oncology · 2012
Influence of enzyme and transporter polymorphisms on trough imatinib concentration and clinical response in chronic myeloid leukemia patients.
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Seong S J, Lim M, Sohn S K, Moon J H, Oh S-J, Kim B S, Ryoo H M, Chung J S, Joo Y D, Bang S M, Jung C W, Kim D H, Park S Y, Yoon S S, Kim I, Lee H G, Won J H, Min Y H, Cheong J W, Park J S, Eom K S, Hyun M S, Kim M K, Kim H, Park M R, Park J, Kim C S, Kim H J, Kim Y K, Park E K, Zang D Y, Jo D Y, Lee H W, Yoon Y-R
Аннотация
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.
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.
Предметные рубрики MeSH
ATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1ATP Binding Cassette Transporter, Subfamily G, Member 2ATP-Binding Cassette TransportersAdolescentAdultAgedAntineoplastic AgentsAryl Hydrocarbon HydroxylasesBenzamidesFemaleGene FrequencyGenotypeHumansImatinib MesylateLeukemia, Myelogenous, Chronic, BCR-ABL PositiveMaleMiddle AgedNeoplasm ProteinsOrganic Cation Transport ProteinsOrganic Cation Transporter 2PiperazinesPolymorphism, Single NucleotidePyrimidinesTreatment OutcomeYoung Adult