Impact of and Polymorphisms on Imatinib Mesylate Response Among Chronic Myeloid Leukemia Patients in Malaysia

Overview

Journal Oncol Ther

Specialty Oncology

Date 2017 Mar 7

PMID 28261657

Citations 12

Authors

Najlaa Maddin

Azlan Husin

Siew Hua Gan

Baba Abdul Aziz

Ravindran Ankathil

Affiliations

Soon will be listed here.

Abstract

Introduction: Imatinib mesylate (IM), a selective inhibitor of the BCR-ABL tyrosine kinase, is a well-established first-line treatment for chronic myeloid leukemia (CML). IM is metabolized mainly by cytochrome P450 (CYP) in the liver, specifically the CYP3A4 and CYP3A5 enzymes. Polymorphisms in these genes can alter the enzyme activity of IM and may affect its response. In this study, the impact of two single-nucleotide polymorphisms (SNPs), (6986A>G) and (878T>C), on IM treatment response in CML patients ( = 270; 139 IM resistant and 131 IM good responders) was investigated.

Methods: Genotyping of and was performed using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) technique. The association between allelic variants and treatment response was assessed by means of odds ratio (OR) with 95% confidence intervals calculated by logistic regression.

Results: Our results indicated that CML patients carrying the heterozygous (AG) and homozygous variant (GG) genotype of *3 were associated with a significantly lower risk of acquiring resistance with OR 0.171; 95% CI: 0.090-0.324, < 0.001 and OR 0.257; 95% CI: 0.126-0.525, < 0.001, respectively. Although CML patients carrying the heterozygous (TC) genotype of showed a lower risk of acquiring resistance toward IM (OR 0.648; 95% CI: 0.277-1.515), the association was not statistically significant ( = 0.316). No homozygous variant (CC) genotype of was detected among the CML patients.

Conclusion: It is concluded that polymorphism of is associated with IM treatment response in Malaysian CML patients with carriers of and genotypes posing lower risk for development of resistance to IM.

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