Imatinib treatment and pharmacogenotype CYP3A4 in relation with the clonal expansion Ph(+) in chronic myeloid leukemia (CML).

Colombia Médica

Mauricio Camargo¹  Olga Zea¹  Domingo Saavedra³  María Isabel Soto Marín² 

[1] Universidad de Antioquia;Universidad de Antioquia.;Clínica Vida

关键词: Imatinib;    Chronic myeloid leucemia;    CML;    CYP3A4;    Philadelphia chromosome;    Pharmacogenetics;    SNPs;   

DOI  :  

学科分类：医学（综合）

来源: Universidad del Valle * Facultad de Salud / Universidad del Valle, Faculty of Health

【 摘 要 】

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.

【 授权许可】

Unknown