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Influence of enzyme and transporter polymorphisms on trough imatinib concentration and clinical response in chronic myeloid leukemia patients
- Source :
- Annals of Oncology. 24:756-760
- Publication Year :
- 2013
- Publisher :
- Elsevier BV, 2013.
-
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.
- Subjects :
- Adult
Male
CYP2D6
ATP Binding Cassette Transporter, Subfamily B
Adolescent
Genotype
Organic Cation Transport Proteins
Antineoplastic Agents
CYP2C19
Pharmacology
Polymorphism, Single Nucleotide
Piperazines
Young Adult
Gene Frequency
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
hemic and lymphatic diseases
ATP Binding Cassette Transporter, Subfamily G, Member 2
Humans
Medicine
Trough Concentration
ATP Binding Cassette Transporter, Subfamily B, Member 1
CYP2C9
Aged
business.industry
Organic Cation Transporter 2
Myeloid leukemia
Imatinib
Hematology
Middle Aged
medicine.disease
Neoplasm Proteins
Leukemia
Pyrimidines
Treatment Outcome
Imatinib mesylate
Oncology
Benzamides
Imatinib Mesylate
ATP-Binding Cassette Transporters
Female
Aryl Hydrocarbon Hydroxylases
business
medicine.drug
Subjects
Details
- ISSN :
- 09237534
- Volume :
- 24
- Database :
- OpenAIRE
- Journal :
- Annals of Oncology
- Accession number :
- edsair.doi.dedup.....c45b8ecea4ac6a0549b23dedbe5fcf67