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Influence of genetic polymorphisms in glutathione-S-transferases gene in response to imatinib among Brazilian patients with chronic myeloid leukemia

Abstract

Polymorphism in metabolizing enzymes can influence drug response as well as the risk for adverse drug reactions. Nevertheless, there are still few studies analyzing the consequence of polymorphisms for the Glutathione-S-transferases (GST) gene to drug response in chronic myeloid leukemia (CML). This study reports, the influence of GSTP1*B and GSTT1/GSTM1null polymorphisms in response to imatinib in CML patients in a Brazilian population. One hundred thirty-nine CML patients from the Clinical Hospital of Goiânia, Goiás, Brazil, treated with imatinib were enrolled in this study. Genotyping of GSTT1 and GSTM1 genes deletions were performed by qPCR and of GSTP1 gene was performed by RFLP-PCR. The frequency of GSTP1*1B, GSTT1 and GSTM1null polymorphisms were determined for all patients. The influence of each patient’s genotypes was analyzed with the patient’s response to imatinib treatment. Brazilian CML patients revealed GSTT1 and GSTM1 genes deletions. GSTT1 deletion was found in 19.3% of patients and GSTM1 deletion in 48.7% of patients with CML. GSTT1/GSTM1 deletion was found in 11.7% in Brazilian CML patients. The “G allele” of GSTP1*B, is associated with later cytogenetic response in imatinib therapy. While, the gene presence combined with GG genotype (GSTM1 present/GSTPI-GG) conferred a tend to a later cytogenetic response to patients. GSTP1*B and GSTT1/GSTM1null polymorphisms influence treatment response in CML. Brazilian CML patients presenting GSTP1 AA/AG genotypes alone and in combination with GSTT1 null reach the cytogenetic response faster, while patients presenting GSTP1-GG and GSTMI positive genotypes may take longer to achieve cytogenetic response. As a result, it allows a better prognosis, with the use of an alternative therapy, other than reducing treatment cost.

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Acknowledgments

The authors would like to express their sincere thanks to the employees of the Clinical Hospital—Federal University of Goiás (UFG) for assisting in the collection of the patient data.

Funding

This study was financially supported by the Foundation for Research Support of the State of Goiás (FAPEG) (Grant No. 08/2009 - PPSUS, to Elisângela de Paula Silveira-Lacerda, Ph.D).

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Contributions

Conceptualization, Kezia Aguiar Delmond, and Elisângela de Paula Silveira-Lacerda.; Methodology, Kezia Aguiar Delmond, Hugo Delleon, AngelaAdamski da Silva Reis, Daniela de Melo e Silva, Elisângela de Paula Silveira-Lacerda.; Software, Kezia Aguiar Delmondand Hugo Delleon.; Validation, Kezia Aguiar Delmond, Hugo Delleon, Daniela de Melo e Silva.; Formal analysis, Kezia Aguiar Delmond, Hugo Delleon, Rebeca Mota Goveiaand Davi Carvalho Abreu.; Investigation, Kezia Aguiar Delmond, Elisângela de Paula Silveira-Lacerda.; resources, Kezia Aguiar Delmond, Adriana do Prado Barbosa, Renato Sampaio Tavares, Carlos Eduardo Anunciação, Elisângela de Paula Silveira-Lacerda.; Data curation, Hugo Delleon, Rebeca Mota Goveia, Thallita Monteiro Teixeira, and Davi Carvalho Abreu.; Writing - Kezia Aguiar Delmond, Elisângela de Paula Silveira-Lacerda.; Writing—review and editing, Kezia Aguiar Delmond, Hugo Delleon, Daniela de Melo e Silva, Francyelli Mello-Andrade, Elisângela de Paula Silveira-Lacerda; Visualization, Kezia Aguiar Delmond, Francyelli Mello-Andrade and Elisângela de Paula Silveira-Lacerda.; Supervision, Elisângela de Paula Silveira-Lacerda.; Project administration, Elisângela de Paula Silveira-Lacerda.; Funding acquisition, Carlos Eduardo Anunciação and Elisângela de Paula Silveira-Lacerda.

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Correspondence to Elisângela Silveira-Lacerda.

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Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was approved by the Ethical Committee of Clinical Hospital of Federal University of Goiás (protocol: 211/2009).

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Patients signed their written informed consent, which was approved by the Ethical Committee of Clinical Hospital of Federal University of Goiás (protocol: 211/2009). The informed consent was obtained from the parent(s)/legally autorized representative (LAR)/guardians of the minors involved in the study. Patients or your parent(s)/LAR/guardians signed informed consent regarding publishing their data.

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Delmond, K.A., Delleon, H., Goveia, R.M. et al. Influence of genetic polymorphisms in glutathione-S-transferases gene in response to imatinib among Brazilian patients with chronic myeloid leukemia. Mol Biol Rep 48, 2035–2046 (2021). https://doi.org/10.1007/s11033-020-06093-z

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Keywords

  • Chronic myeloid leukemia
  • Cytogenetic response
  • GST
  • Imatinib
  • Personalized medicine