TITLE:
Polymorphism of Human Organic Cationic Transporter1 (C480G) in Egyptian Chronic Myeloid Leukemia Patients on Imatinib
AUTHORS:
Nahla A. M. Hamed, Hashim Neanea, Amal M. Ghanem, Maha M. A. Elgammal, Yasmen Samir
KEYWORDS:
Chronic Myeloid Leukemia, Imatinib, Egyptian, Resistance, Human Organic Cationic Transporter1 C480G Polymorphism
JOURNAL NAME:
American Journal of Molecular Biology,
Vol.8 No.2,
April
11,
2018
ABSTRACT: Background: Human organic
cationic transporter1 (Hoct1) is a plasma membrane transporter responsible for
the main influx of Imatinib into chronic myeloid leukemia (CML) cells. Single
nucleotide polymorphisms (SNPs) in the gene coding for hOCT1 are important
factors causing Imatinib resistance. We investigated the frequency of hOCT1 SNP
C480G among Egyptian CML patients and its relation to early molecular response
as an indicator of treatment outcome. Materials and Methods: Two groups of CML patients were included in this study. Group I consisted
of 25 patients responding to Imatinib treatment (Imatinib responsive) and group
II consisted of 25 patients resistant to Imatinib (Imatinib resistant).
Response criteria were assessed according to the NCCN (National Comprehensive
Cancer Network) guidelines 2017. Twenty healthy controls of matched age and sex
were also included (group III). For all patients, we studied hOCT1 C480G at
initial presentation using Taqman drug metabolism genotyping as well as
BCR-ABL percent at diagnosis and after 3 months interval. Results: hOCT1
C480G was present in 32% of studied CML patients. CC (wild) was detected in 68%
of group I and 64% of group II. CG (mutant heterozygous) was present in 28% of
group I and 36% of group II while GG (mutant homozygous) was detected in only
one case in group I. CG was also detected in 15% of control subjects
There was no significant difference between hOCT1 C480G polymorphism and Early
Molecular Response (χ2 = 0.089, p = 0.765). Conclusions: hOCT1 C480G polymorphism has no
association with Imatinib resistance in Egyptian population. However, further
studies on a larger number of patients are still needed to confirm this finding.