TITLE:
MDR1 Haplotypes and G2677T/A Polymorphism Predict Imatinib Response in Tunisian Patients with Chronic Myeloid Leukemia
AUTHORS:
Mariam Ammar, Sonia Ktari, Moez Medhaffar, Hanen Ghozzi, Moez Elloumi, Adnen Hammami, Khaled Zeghal, Lobna Ben Mahmoud
KEYWORDS:
Chronic Myeloid Leukemia, Imatinib Mesylate, P-Glycoprotein, Multi Drug Resistance, G2677T/A, Haplotype
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.10 No.9,
September
14,
2022
ABSTRACT: Background: The role of human multidrug resistance gene (MDR1) SNPs in the interindividual variability of imatinib mesylate (IM) response has received considerable attention. We aimed to study the association between SNPs of the MDR1 gene (C1236T, G2677T/A, C3435T) and IM response in chronic myeloid leukemia (CML) patients. Method: A retrospective case-control study was conducted on 48 patients with CML undergoing IM therapy. All patients were genotyped using PCR-RFLP method. Results: The genotype and allele frequencies of C1236T and C3435T were not significantly different between CML patients responders and non-responders to IM (p > 0.05). The frequencies of 2677T allele and 2677TT genotype were significantly increased in CML patients IM responders which as compared with IM non-responders (50% vs 26.9%, p = 0.013 and 27.3% vs 3.8%, p = 0.029 respectively). Whereas the 2677AA genotype and CAC haplotype were found only in CML patients IM non-responders (15.4%). Conclusion:Pretreatment genotyping of G2677A/T appears to be useful for predicting IM resistance, which may allow the best choice of drug treatment for CML patients.