Genetic Variants in Oxidative Stress-Related Genes and Their Impact on Prognosis and Treatment Response in Chronic Myeloid Leukemia Patients

Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasia characterized by the <i>BCR::ABL1</i> 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 <i>SOD2</i>, <i>CAT GPX1</i>, <i>NRF2</i>, and <i>KEAP1</i> genetic variants with TKI response and disease prognosis. For this purpose, we genotyped the variants rs4880 (<i>SOD2</i>), rs1050450 (<i>GPX1</i>), rs1001179 (<i>CAT</i>), rs6721961, rs4893819, rs35652124, rs6706649, rs13001694 (<i>NFE2L2</i>), and rs113540846 (<i>KEAP1</i>) 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 <i>GPX1</i> and CT genotype of <i>NFE2L2</i> rs4893819), the appearance of mutations in the <i>BCR::ABL1</i> gene (AG genotype of <i>NFE2L2</i> rs13001694 and genetic profile GGCTTCCCGG of the <i>NFE2L2</i>/<i>KEAP1</i> axis), disease evolution (AG genotype of <i>SOD2</i> and CT genotype of <i>NFE2L2</i> rs4893819), and overall survival (CC genotype of <i>CAT</i> and GG genotype of <i>NFE2L2</i> rs13001694) of CML patients. Our study found that variants in oxidative stress-related genes impact treatment response and outcomes in CML.