Author(s):
Alves, Raquel ; Ventura, Filipa ; Jorge, Joana ; Marques, Gilberto ; Coucelo, Margarida ; Diamond, Joana ; Oliveiros, Bárbara ; Pereira, Amélia ; Freitas-Tavares, Paulo ; Almeida, António M. ; Gonçalves, Ana Cristina ; Sarmento-Ribeiro, Ana Bela
Date: 2025
Persistent ID: http://hdl.handle.net/10400.14/54588
Origin: Veritati - Repositório Institucional da Universidade Católica Portuguesa
Subject(s): Antioxidant defenses; Chromic myeloid leukemia; Genetic variants; NRF2/KEAP1 pathway; Overall survival; Tyrosine kinase inhibitor resistance
Description
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.
