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Variants in vincristine pharmacodynamic genes involved in neurotoxicity at induction phase in the therapy of pediatric acute lymphoblastic leukemia

The Pharmacogenomics Journal volume 19, pages 564–569 (2019)Cite this article

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Abstract

Vincristine is an important drug of acute lymphoblastic leukemia (ALL) treatment protocols that can cause neurotoxicity. Patients treated with LAL/SHOP protocols often suffer from vincristine-related neurotoxicity in early phases of treatment. A genetic variant in CEP72, a gene involved in vincristine pharmacodynamics, was recently associated with neurotoxicity after prolonged vincristine treatment. This association was not replicated in our Spanish population during induction phase. To test the possibility that other variants in genes involved in vincristine pharmacodynamics were associated with vincristine neuropathy in early phases of the treatment, we evaluated the correlation with toxicity of 24 polymorphisms in 9 key genes in a large cohort of 152 Spanish children with B-ALL homogeneously treated. Results showed no association between any genetic variant in the TUBB1, TUBB2A, TUBB2B, TUBB3, TUBB4, MAPT, MIR146a, MIR202, and MIR411 genes and vincristine-related neurotoxicity. These results are in line with the hypothesis that there are different mechanisms causing pheripheral neurotoxicity after prolonged and short-term vincristine treatments.

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Acknowledgements

This project was supported by the Basque Government (IT989–16, IT661–13, and 2012111053). A.G.-C. was supported by a predoctoral grant from the Basque Government (Programa de Formación de Personal Investigador no doctor). Supported by the Spanish National Genotyping Center (CeGen) is gratefully acknowledged.

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Authors and Affiliations

  1. Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Medicine and Nursery, University of the Basque Country (UPV/EHU), Leioa, Spain

    Idoia Martin-Guerrero, Angela Gutierrez-Camino & Africa Garcia-Orad

  2. Unit of Pediatric Hematology/Oncology, University Hospital Cruces, Bilbao, Spain

    Aizpea Echebarria-Barona & Itziar Astigarraga

  3. BioCruces Health Research Institute, Barakaldo, Spain

    Aizpea Echebarria-Barona, Itziar Astigarraga, Aurora Navajas & Africa Garcia-Orad

  4. Department of Pediatrics, Faculty of Medicine and Nursery, University of the Basque Country (UPV/EHU), Leioa, Spain

    Itziar Astigarraga & Aurora Navajas

  5. Unit of Pediatric Oncohematology, University Hospital Donostia, San Sebastian, Spain

    Nagore Garcia de Andoin

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  1. Idoia Martin-Guerrero
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  2. Angela Gutierrez-Camino
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Correspondence to Africa Garcia-Orad.

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Martin-Guerrero, I., Gutierrez-Camino, A., Echebarria-Barona, A. et al. Variants in vincristine pharmacodynamic genes involved in neurotoxicity at induction phase in the therapy of pediatric acute lymphoblastic leukemia. Pharmacogenomics J 19, 564–569 (2019). https://doi.org/10.1038/s41397-019-0081-5

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