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OCT-1 Expression in Patients with Chronic Myeloid Leukemia: A Comparative Analysis with Respect to Response to Imatinib Treatment

Abstract

The introduction of tyrosine kinase inhibitors (TKI) has resulted in a significant improvement in the treatment of CML patients. However, some CML patients are resistant to imatinib therapy, the initial TKI therapy in the CML. Therefore, it is important to find prognostic markers for resistance. The OCT-1 gene involved in imatinib uptake is also suspected to cause imatinib resistance. The aim of this study was to investigate the role of OCT-1 in imatinib resistance by comparing OCT-1 expression levels in imatinib resistant and imatinib sensitive patients with chronic myeloid leukemia (CML). This study was conducted on 101 patients with CML [imatinib sensitive (n = 51) and imatinib resistant (n = 50)] who were treated with imatinib. Gene expression analysis was done using QRT-PCR. The relative expression levels of OCT-1 were calculated using 2(−ΔΔCT) method. OCT1 mRNA expression levels were 0.149 (0.011–2.532) and 0.119 (0.008–2.868) in imatinib-sensitive group and imatinib-resistant group, respectively. OCT-1 expression levels were not significantly different in the imatinib-sensitive group when compared to imatinib resistant group (p > 0.05). OCT-1 expression was also similar in BCR-ABL1 kinase domain mutation positive and negative cases (p > 0.05). The imatinib-resistant group had a higher rate of hydroxyurea or interferon-alpha treatment prior to imatinib therapy and a lower rate for first-line imatinib as the only treatment than the imatinib-sensitive group (p = 0.002 and p = 0.002, respectively). According to the results of our study, OCT-1 does not have a biomarker feature in the evaluation of imatinib response. In addition, the study should be performed in larger patient groups.

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Acknowledgements

The study was supported by the İstanbul University Scientific Research Foundation (Project Number: 57862).

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Correspondence to Aynur Daglar Aday.

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Ethıcal Approval

The study was conducted in accordance with the ethical principles stated in the “Declaration of Helsinki”. The study was approved by the Clinical Research Ethics Committee of the Istanbul Medical Faculty, Istanbul University (Decision number/date: 1330/June 26, 2015).

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Written informed consent was obtained from each subject following a detailed explanation of the objectives and protocol of the study.

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Bozkurt Bulakcı, B., Daglar Aday, A., Gurtekin, B. et al. OCT-1 Expression in Patients with Chronic Myeloid Leukemia: A Comparative Analysis with Respect to Response to Imatinib Treatment. Indian J Hematol Blood Transfus 38, 668–674 (2022). https://doi.org/10.1007/s12288-022-01532-2

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  • DOI: https://doi.org/10.1007/s12288-022-01532-2

Keywords

  • Chronic myeloid leukemia
  • Imatinib
  • Resistance
  • OCT-1