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Detection of mutations in CML patients resistant to tyrosine kinase inhibitor: imatinib mesylate therapy

Medical Oncology volume 38, Article number: 120 (2021) Cite this article

Abstract

Imatinib mesylate, a tyrosine kinase inhibitor, is the first choice in chronic myeloid leukemia treatment. However, resistance to imatinib may develop with time and in some cases, patients may not respond at all to imatinib. Progressive resistance to imatinib therapy is often due to mutations in the BCR/ABL region. Within the scope of our study 124 patients were evaluated via pyrosequencing between 2015 and 2020. In this regard, 32 patients who have a partial response and have no response to imatinib therapy were included in the study. In addition, next-generation sequencing (NGS) analysis was performed on 15 patients who were resistant to imatinib treatment according to the molecular follow-up reports. With pyrosequencing, 5 cases out of a total of 124 were found to be positive. This means that approximately 4.03% of the proportion is positive. But when we examined only 32 patients who have a partial response and have no response to imatinib therapy this rate is rising 15.6%. NGS analysis was performed with 15 patients who have no mutation with pyrosequencing of 32 patients and VUS (Variant of Uncertain Significance) mutation was detected in one. In this study, our aim was to determine the mutations of the BCR/ABL and to evaluate the mutations by NGS and pyrosequencing. Our study is important in terms of comparing the pyrosequencing with NGS mutation rates, drawing attention to the clinical importance of log reduction.

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Data availability

All data are available upon request.

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Acknowledgements

The results reported in this article were partially presented at the 7th International Congress of Pharmaceutical Chemistry: API Design, Synthesis, Production, and Standardization, on March 14–17, 2019.

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Authors and Affiliations

  1. Department of Medical Genetics, Faculty of Medicine, Erciyes University, Kayseri, Turkey

    Nilgun Karasu, Hilal Akalin, Nuriye Gokce, Abdulbaki Yildirim, Mikail Demir, Hande Kulak & Munis Dundar

  2. Department of Hematology, Faculty of Medicine, Erciyes University, Kayseri, Turkey

    Serhat Celik & Muzaffer Keklik

Authors
  1. Nilgun Karasu
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  2. Hilal Akalin
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  3. Nuriye Gokce
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  6. Hande Kulak
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Contributions

MD* developed the theory and concept of the study. HA designed the study. NK produced the first draft and completed the entire manuscript. NG carried out the NGS laboratory studies and performed the statistical analysis. HK analyzed the patient’s data. AY conducted the literature search. MK and SC provided clinical information of patients. MD evaluated the clinical results and contributed to the lettering of the manuscript. All the authors collected patient data and read and approved the final manuscript (*: corresponder).

Corresponding author

Correspondence to Munis Dundar.

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Conflict of interest

The authors have no conflicts of interest to disclose.

Ethical approval

This study was approved with the decision dated Dec 16th, 2020 and numbered 629 by Erciyes University Clinical Research Ethics Committee.

Informed consent

All participants gave written informed consent in accordance with the Declaration of Helsinki.

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Karasu, N., Akalin, H., Gokce, N. et al. Detection of mutations in CML patients resistant to tyrosine kinase inhibitor: imatinib mesylate therapy. Med Oncol 38, 120 (2021). https://doi.org/10.1007/s12032-021-01571-1

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  • DOI: https://doi.org/10.1007/s12032-021-01571-1

Keywords

  • CML
  • Fusion gene BCR/ABL
  • T315I
  • Imatinib resistance
  • NGS