Author/Authors :
Khosravi, M Department of Genetics and Molecular Biology - Faculty of Medicine - Isfahan University of Medical Sciences - Isfahan, Islamic Republic of Iran , Khalaj, Z Cancer Prevention Research Center - Isfahan University of Medical Sciences - Isfahan, Islamic Republic of Iran , Nouri, N Cancer Prevention Research Center - Isfahan University of Medical Sciences - Isfahan, Islamic Republic of Iran , Najaflu, M Cancer Prevention Research Center - Isfahan University of Medical Sciences - Isfahan, Islamic Republic of Iran , Mehrzad, V Cancer Prevention Research Center - Isfahan University of Medical Sciences - Isfahan, Islamic Republic of Iran , Forat-yazdi, M Department of Internal Medicine - Faculty of Medicine - Shahid Sadoughi University of Medical Sciences - Yazd, Islamic Republic of Iran , Mokarian, F Cancer Prevention Research Center - Isfahan University of Medical Sciences - Isfahan, Islamic Republic of Iran , Salehi, M Department of Genetics and Molecular Biology - Faculty of Medicine - Isfahan University of Medical Sciences - Isfahan, Islamic Republic of Iran
Abstract :
Imatinib introduction caused to improve the clinical outcomes of chronic myeloid
leukemia (CML) patients. Despite the significant effects of Imatinib, pharmacogenetic
variables induced treatment resistant is also observed. Imatinib is known as a Pglycoprotein
(P-gp) efflux pump substrate encoded by the ABCB1 gene. The ABCB1
C1236T, G2677T/A and C3435T variants are possibly correlated with interindividual
variation in pharmacokinetic response to Imatinib therapy. The present study aimed to
examine the effect of ABCB1 gene variants on the therapeutic response of Imatinib in
CML patients. Sixty-nine Iranian CML patients treated with Imatinib or Nilotinib were
selected and divided into two groups of sensitive and resistant to Imatinib. C1236T and
G2677T/A variants were genotyped by high resolution melting (HRM) analysis, and
C3435T variant was genotyped using polymerase chain reaction–restriction fragment
length polymorphism (PCR-RFLP). Then, the results were compared between the two
groups of patients. Our results showed that there were no significant differences
between C1236T, G2677T/A and C3435T variants of ABCB1 gene and clinical
response to Imatinib in the Iranian CML patients. According to the results of this study,
genotyping of ABCB1 C1236T, G2677T/A and C3435T variants couldn’t help to
predict the outcomes of Imatinib treatment in CML patients. So, these variants are not useful to
make decisions about treatment, but it is suggested to do further investigations.
Keywords :
Variants , Imatinib mesylate , Chronic myeloid leukemia , ABCB1