Imatinib treatment and pharmacogenotype CYP3A4 in relation with the clonal expansion Ph(+) in chronic myeloid leukemia (CML).
Abstract
Introduction: Imatinib is an inhibitor of the BCR-ABL tyrosine-kinase that has dramatically changed the treatment of patient with Chronic myeloid leukemia (CML) positive for the Philadelphia chromosome (Ph+). This compound is mainly metabolized by the cytochrome CYP3A4 enzyme, coded by a gene with individual variations that could interfere with the effectiveness of the treatment, due to the fact that particular single nucleotide polymorphisms (SNPs), i.e., CYP3A4*1B y CYP3A4*2, have shown to exert a significant influence on the metabolic activity of this pharmacologically important enzyme.Objective: Evaluate the frequency of pharmacogenetically important polymorphisms in the CYP3A4 gen in a Colombian population of patients with CML being treated with this novel drug (Imatinib), in parallel with a control population of 164 healthy individuals. Correlate the evolution of the clonal expansion Ph(+) with the presence of these SNPs and the length of treatment.
Methodology: PCR-RFLP genotyping for the CYP3A4* 1B y CYP3A4*2 SNPs. RBHG replication banding for the evaluation of the presence of the Ph(+) markers in spontaneous mitotic blasts.
Results: A positive cytogenetic response and/or correlation was detected between the length of the imatinib treatment and a reduction in the percentage of Ph(+) blasts. Genotyping indicate that CYP3A4*1B polymorphism does no affect the cytogenetic response in imatinib treated Ph(+) patients, and that the pharmacorelevant CYP3A4*2 SNP is not present in this population of patients and controls (N=194).
Conclusions: The pharmacogenotype CYP3A4*2 (exon 7) does not affect the induced positive cytogenetic response triggered by the imatinib treatment, that generally induces a reduction in Ph(+) blasts en relation with the duration of the treatment.
Authors
Downloads
Download data is not yet available.
Keywords
- Imatinib
- Chronic myeloid leucemia
- CML
- CYP3A4
- Philadelphia chromosome
- Pharmacogenetics
- SNPs
Submitted
2009-12-02
|
502 |
How to Cite
Camargo, M., Soto Marín, M. I., Zea, O., & Saavedra, D. (1). Imatinib treatment and pharmacogenotype CYP3A4 in relation with the clonal expansion Ph(+) in chronic myeloid leukemia (CML). Colombia Médica, 39(4), 314-322. https://doi.org/10.25100/cm.v39i4.613
Issue
Section
Original Articles
The copy rights of the articles published in Colombia Médica belong to the Universidad del Valle. The contents of the articles that appear in the Journal are exclusively the responsibility of the authors and do not necessarily reflect the opinions of the Editorial Committee of the Journal. It is allowed to reproduce the material published in Colombia Médica without prior authorization for non-commercial use