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Influence of enzyme and transporter polymorphisms on trough imatinib concentration and clinical response in chronic myeloid leukemia patients.

Authors
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
Citation
Annals of oncology : official journal of the European Society for Medical Oncology, 24(3):756-760, 2013
Journal Title
Annals of oncology : official journal of the European Society for Medical Oncology
ISSN
0923-75341569-8041
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.
MeSH terms
ATP-Binding Cassette Transporters/geneticsAdolescentAdultAgedAntineoplastic Agents/*pharmacokineticsAryl Hydrocarbon Hydroxylases/geneticsBenzamides/*pharmacokineticsFemaleGene FrequencyGenotypeHumansLeukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy/enzymology/*geneticsMaleMiddle AgedNeoplasm Proteins/geneticsOrganic Cation Transport Proteins/geneticsP-Glycoprotein/geneticsPiperazines/*pharmacokinetics*Polymorphism, Single NucleotidePyrimidines/*pharmacokineticsTreatment OutcomeYoung Adult
DOI
10.1093/annonc/mds532
PMID
23117072
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Hematology-Oncology
AJOU Authors
박, 준성
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