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EFFECT OF OCT1 GENE POLYMORPHISM ON RESPONSE TO IMATINIB MESYLATE IN CML PATIENTS

PB1919

Sabri, A.1; Omran, M.2; Abdel Azim, S.3; Abdelfatah, R.4; Shouman, S.2

doi: 10.1097/01.HS9.0000566176.59245.aa
Publication Only: Chronic myeloid leukemia - Biology & translational research
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1Egyptian Pharmaceutical Vigilance Center, Central Administration of Pharmaceutical Affairs

2Cancer Biology Department-Pharmacology Unit, National Cancer Institute, Cairo University

3Biochemistry Department, Faculty of Pharmacy, Cairo University

4Medical oncology department, National Cancer Institute, Cairo University, Cairo, Egypt

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Background:

Imatinib mesylate (IM) has been shown to be highly efficacious in the treatment of Chronic Myeloid Leukemia (CML). Continuous and adequate dosing is essential for optimal outcomes. There is a considerable variability in the level of molecular responses achieved with IM therapy. These differences could result from variable drug level which may be due to genetic factors.

The human organic cation transporter 1 (OCT1; SLC22A1) has been reported to be the main influx transporter responsible for active uptake of IM into CML cells.

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Aims:

We hypothesized that the SNPs of this gene could predict the outcomes of IM therapy in CML patients.

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Methods:

Fifty patients with CML at chronic phase were studied. All patients were monitored at outpatient clinic of the National Cancer Institute, Cairo University, Egypt. The study was approved by the NCI Ethical Committee for Clinical Research. Written Informed consent was obtained. The polymorphism of SLC22A1 gene was studied using PCR-RFLP technique. Imatinib mesylate level was determined using HPLC-massspectroscopy.

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Results:

The mean IM trough plasma level in patients who achieved unfavorable response (n = 25) was 1019 ± 638 ng/mL, and in patients who achieved favorable response (n = 25) 1353 ± 611 ng/mL (p=0.04).

In regard to SLC22A1 rs(628031) gene, heterogeneous & variant allele (GA&AA) was significantly correlated to unfavorable response while wild allele GG is linked to favorable response(p=0.0006).

No significant correlation was detected between SLC22A1 gene polymorphism and drug level (p=0.08).

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Summary/Conclusion:

In patients with CML treated with IM, one of the significant factors affecting response was OCT1 polymorphism. This may influence the interindividual variation observed among Egyptian CML patients. Although a prospective study with a larger patient population is necessary to validate this finding.

In patients with CML treated with IM, one of the significant factors affecting response was OCT1 polymorphism. This may influence the interindividual variation observed among Egyptian CML patients. Although a prospective study with a larger patient population is necessary to validate this finding.

Copyright © 2019 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the European Hematology Association.