Document Type : Original Article(s)
Authors
- Nesma Elshahat 1
- Sahar Kamal 1
- Somaia Mohamed Mousa 1
- Hend Nabil Ellithy 2
- Shirihan Mahmoud Mahgoub 1
- Mohamed Fateen 1
1 Department of Clinical Pathology, Kasr Al-Ainy Faculty of Medicine, Cairo University, Cairo, Egypt
2 Clinical Hematology Unit, Department of Internal Medicine, Kasr Al-Ainy Faculty of Medicine, Cairo University, Cairo, Egypt
Abstract
Background: Human organic cation transporter 1 (hOCT1) encoded by the SLC22A1 gene, mediates uptake of imatinib (a tyrosine kinase inhibitor) into chronic myeloid leukemia (CML) cells. Variants in hOCT1 genes have been proposed to influence treatment outcomes. This study aimed to determine whether the hOCT1 variants M408V (rs628031) and M420del (rs35191146) are associated with early molecular response to imatinib in patients with CML.
Method: This cohort study included 60 CML patients who had received imatinib therapy for six months. Genotyping of M408V was performed using real-time polymerase chain reaction (PCR), while M420del was analyzed by allele-specific PCR. Patients were stratified according to Sokal and ELTS risk scores, and molecular response was assessed using quantitative BCR::ABL1 transcript levels. Statistical analysis was performed using International Business Machines-Statistical Package for the Social Sciences (IBM SPSS) version 28. Associations between genotypes and treatment response were evaluated using the Chi-square test or Fisher’s exact test, and logistic regression analysis was used to estimate odds ratios and 95% confidence intervals. A P-value <0.05 was considered to be statistically significant.
Results: At six months of therapy, 38.33% of patients were classified as optimal responders, while 61.67% were suboptimal/non-responders. No statistically significant association was found between M408V or M420del genotypes and early molecular response to imatinib. However, both Sokal and ELTS scores were predictive of response, with the Sokal score showing superior performance in identifying non-responders.
Conclusion: The M408V and M420del variants of hOCT1 were not associated with early molecular response to imatinib therapy in this cohort of CML patients. Risk stratification scores, particularly the Sokal score, remain valuable predictors of treatment response.
Highlights
Somaia Mohamed Mousa (google scholar)
Keywords
- Organic cation transporter 1
- Chronic myeloid leukemia
- Imatinib
- Single nucleotide polymorphism
- Treatment outcome
Main Subjects
Please cite this article as: Elshahat N, Kamal S, Mousa SM, Ellithy HN, Mahgoub SM, Fateen M. Genetic Variants of Human Organic Cation Transporter1 (hOCT1) -M408V and M420del- Are Not Associated with Imatinib Response in Chronic Myeloid Leukemia. Middle East J Cancer. 2026: in press. doi: 10.30476/mejc.2026.110821.2414.
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