Can pharmacogenetics impact the therapeutic effect of cytarabine and anthracyclines in adult acute myeloid leukaemia patients? A Serbian experience

  • Zlatko Pravdić Clinic of Hematology, University Clinical Centre of Serbia, Belgrade
  • Marijana Virijević Clinic of Hematology, University Clinical Centre of Serbia, Belgrade; Faculty of Medicine, University of Belgrade, Belgrade, Serbia
  • Mirjana Mitrović Clinic of Hematology, University Clinical Centre of Serbia, Belgrade; Faculty of Medicine, University of Belgrade, Belgrade, Serbia
  • Nikola Pantić Clinic of Hematology, University Clinical Centre of Serbia, Belgrade
  • Nikica Sabljić Clinic of Hematology, University Clinical Centre of Serbia, Belgrade
  • Đorđe Pavlović Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia
  • Irena Marjanović
  • Zoran Bukumirić Institute of Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
  • Ana Vidović Clinic of Hematology, University Clinical Centre of Serbia, Belgrade; Faculty of Medicine, University of Belgrade, Belgrade, Serbia
  • Ljubomir Jaković Clinic of Hematology, University Clinical Centre of Serbia, Belgrade
  • Sonja Pavlović Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia
  • Nada Suvajdžić Clinic of Hematology, University Clinical Centre of Serbia, Belgrade; Faculty of Medicine, University of Belgrade, Belgrade, Serbia
  • Vladimir Gasic Institute of Molecular Genetics and Genetic Engineering
DOI: https://doi.org/10.5937/jomb0-47459
Keywords: AML, Anthracyclines, Cytarabine, Pharmacogenetic variants

Abstract


Background. Cytarabine-anthracycline based induction chemotherapy remains the standard of care for remission induction among patients with newly diagnosed acute myeloid leukaemia (AML). There are remarkable differences in therapy response among AML patients. This fact could be partly explained by the patients’ genetic variability related to metabolic paths of cytarabine and anthracyclines. The aim of this study is to evaluate the effect of variants in pharmacogenes SLC29A1, DCK, ABCB1, GSTM1 and GSTT1, as well as laboratory and AML-related parameters on clinical outcome in adult AML patients.

Methods. A total of 100 AML patients were included in the study. Pharmacogenetic variants SLC29A1 rs9394992, DCK rs12648166, ABCB1 rs2032582 and GSTM1 and GSTT1 gene deletions were detected by methodology based on PCR, fragment analysis and direct sequencing. The methods of descriptive and analytic statistics were used. Survival analysis was done by the Kaplan-Meier method using the Log-Rank test.

Results. This is the first study of adult AML pharmacogenetics in Serbian population. Clinical outcomes in our cohort of AML patients were not impacted by analysed variants in SLC29A1, DCK, ABCB1and GSTT1 and GSTM1 genes, independently or in combinations. Achievement of complete remission was identified as an independent prognostic indicator of clinical outcome.

Conclusions. The population specific genomic profile has to be considered in pharmacogenetics. Since the data on AML pharmacogenetics in European populations is limited, our results contribute to knowledge in this field and strongly indicate that high-throughput approach has to be applied in order to find particular pharmacogenetic markers of AML in European population.

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Published
2024/04/26
Issue
Ahead of print
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Original paper

Copyright (c) 2024 Zlatko Pravdic, Marijana Virijević, Mirjana Mitrović, Nikola Pantić, Nikica Sabljić, Đorđe Pavlović, Irena Marjanović, Zoran Bukumirić, Ana Vidović, Ljubomir Jaković, Sonja Pavlović, Nada Suvajdžić, Vladimir Gasic

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