Ankathil, Ravindran
(2016)
Imatinab mesylate treatment in Chronic Myeloid
Leukemia (CML)- understanding the
fundamental pharmacokinetic and
pharmacogenetic mechanisms for variation in
response.
Project Report.
Pusat Pengajian Sains Perubatan, Universiti Sains Malaysia.
(Submitted)
Abstract
Although lmatinib mesylate (IM) is the gold standard drug for Chronic Myeloid Leukemia (CML)
treatment, resistance to IM emerges in a significant number of patients. Resistance could be due to
several factors. Pharmacokinetic variability as a result of genetic polymorphisms in IM metabolizing
genes could be a potential factor. This study was undertaken to investigate the genotype frequencies
and the impact of ORM1 520G>A, PXR 1792A>G, CAR 540C>T, CYP3A4 878T>C and CYP3A5
6986A>G polymorphisms towards CML susceptibility risk and IM response. A total of 540 subjects (270
CML patients and 250 normal healthy controls) have been recruited in this study. Genotyping was
performed and the association between allelic variants and CML susceptibility risk and response to IM
treatment were assessed by means of odds ratio (OR) with 95% confident interval s calculated by
logistic regression. Results showed that PXR 1792A>G, CAR 540C>T and CYP3A5 6986A>G were
significantly associated with IM responses and CAR 540C>T, CYP3A4 878T>C and CYP3A5 6986A>G
were significantly associated with CML susceptibility risk. Further study should be done on a larger
scale to validate whether this polymorphism can be used as a predictive biomarker for identifying
resistance development among CML patients undergoing IM treatment.
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