hOCT1 gene expression predict for optimal response to Imatinib in Tunisian patients with chronic myeloid leukemia
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Imatinib mesylate (IM) is considered as a highly effective therapy for chronic myeloid leukemia (CML) patients. However, a minority of patients fail to achieve optimal response due to impaired bioavailability of IM. The human organic cation transporter 1 (OCT1; SLC22A1) has been reported to be the main influx transporter involved in IM uptake into CML cells. Genetic variants and/or hOCT1 expression changes may influence IM response. In this study, we aimed to investigate the impact of both hOCT1 polymorphisms located in exon 7 and hOCT1 mRNA levels on the clinical outcome in CML patients.
hOCT1 expression profile was determined using the quantitative real-time polymerase chain reaction in 69 CML patients treated with IM (35 responders to IM patients and 34 IM-resistant patients), while genotyping of 69 cases and 51 controls for hOCT1 polymorphisms was performed by direct sequencing after amplification of exon7.
Our results showed that the hOCT1 gene was significantly downregulated in the samples of the IM-resistant group when compared with the IM-responder group (p = 0.0211). Moreover, sequencing data show an association in all cases between the SNP 408V>M (g.1222G>A) and an intronic 8 bp (base pairs) insertion of GTAAGTTG (rs36056065) at the 3′ end of exon 7. The genotype and allele distribution of the different SNPs did not differ significantly between the two groups of patients.
hOCT1 mRNA expression may serve as a clinical biomarker of response to imatinib and could be useful to predict IM therapy outcome of CML patients.
KeywordsChronic myeloid leukemia Imatinib mesylate Resistance hOCT1 Expression Polymorphisms
We wish to thank all the staff members of the Laboratory of Molecular and Cellular Hematology, Pasteur Institute of Tunis (LR11 IPT07). This work was supported by the Ministry of Higher Education and Scientific Research in Tunisia.
Compliance with ethical standards
Conflict of interest
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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