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

## TL;DR

This study explores how genetic variations in oxidative stress-related genes affect treatment response and survival in chronic myeloid leukemia patients.

## Contribution

The study identifies specific genetic variants linked to tyrosine kinase inhibitor resistance and prognosis in CML patients.

## Key findings

- Variants in SOD2, GPX1, CAT, NRF2, and KEAP1 genes influence TKI resistance and disease progression in CML.
- Certain genotypes are associated with BCR::ABL1 mutations and overall survival rates in CML patients.
- Genetic profiles of the NFE2L2/KEAP1 axis correlate with treatment outcomes and disease evolution.

## 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.