Genetic variants in oxidative stress-related genes and their impact on prognosis and treatment response in chronic myeloid leukemia patients

Raquel Alves, Filipa Ventura, Joana Jorge, Gilberto Marques, Margarida Coucelo, Joana Diamond, Bárbara Oliveiros, Amélia Pereira, Paulo Freitas-Tavares, António M. Almeida, Ana Cristina Gonçalves*, Ana Bela Sarmento-Ribeiro

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasia characterized by the BCR::ABL1 fusion gene, which codifies the BCR-ABL protein with increased tyrosine kinase activity. Despite the clinical results for the outstanding tyrosine kinase inhibitors (TKIs), drug resistance is a problem in CML management. Genetic variants that alter redox homeostasis by changing antioxidant enzyme expression or activity may influence patient responses and could enhance patient stratification. We aimed to assess the association of SOD2, CAT GPX1, NRF2, and KEAP1 genetic variants with TKI response and disease prognosis. For this purpose, we genotyped the variants rs4880 (SOD2), rs1050450 (GPX1), rs1001179 (CAT), rs6721961, rs4893819, rs35652124, rs6706649, rs13001694 (NFE2L2), and rs113540846 (KEAP1) via PCR in 187 CML patients. Our results show that variants in genes related to oxidative stress influence the development and degree of TKI resistance (allele G and GG genotypes of GPX1 and CT genotype of NFE2L2 rs4893819), the appearance of mutations in the BCR::ABL1 gene (AG genotype of NFE2L2 rs13001694 and genetic profile GGCTTCCCGG of the NFE2L2/KEAP1 axis), disease evolution (AG genotype of SOD2 and CT genotype of NFE2L2 rs4893819), and overall survival (CC genotype of CAT and GG genotype of NFE2L2 rs13001694) of CML patients. Our study found that variants in oxidative stress-related genes impact treatment response and outcomes in CML.
Original languageEnglish
Article number5682
Number of pages15
JournalInternational Journal of Molecular Sciences
Volume26
Issue number12
DOIs
Publication statusPublished - 13 Jun 2025

Keywords

  • Antioxidant defenses
  • Chromic myeloid leukemia
  • Genetic variants
  • NRF2/KEAP1 pathway
  • Overall survival
  • Tyrosine kinase inhibitor resistance

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