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
Laboratory of Oncobiology and Hematology (LOH) and University Clinics of Hematology and Oncology, Faculty of Medicine University of Coimbra (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal.
Coimbra Institute for Clinical and Biomedical Research (iCBR)-Group of Environmental Genetics of Oncobiology (CIMAGO), Faculty of Medicine University of Coimbra (FMUC), University of Coimbra, 3000-548 Coimbra, Portugal.
Int J Mol Sci. 2025 Jun 13;26(12):5682. doi: 10.3390/ijms26125682.
Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasia characterized by the 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 , , , and genetic variants with TKI response and disease prognosis. For this purpose, we genotyped the variants rs4880 (), rs1050450 (), rs1001179 (), rs6721961, rs4893819, rs35652124, rs6706649, rs13001694 (), and rs113540846 () 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 and CT genotype of rs4893819), the appearance of mutations in the gene (AG genotype of rs13001694 and genetic profile GGCTTCCCGG of the / axis), disease evolution (AG genotype of and CT genotype of rs4893819), and overall survival (CC genotype of and GG genotype of rs13001694) of CML patients. Our study found that variants in oxidative stress-related genes impact treatment response and outcomes in CML.
慢性髓性白血病（CML）是一种克隆性骨髓增殖性肿瘤，其特征在于融合基因，该基因编码具有增加的酪氨酸激酶活性的BCR-ABL蛋白。尽管酪氨酸激酶抑制剂（TKIs）取得了显著的临床效果，但耐药性仍是CML治疗中的一个问题。通过改变抗氧化酶表达或活性来改变氧化还原稳态的基因变异可能会影响患者的反应，并可增强患者分层。我们旨在评估[具体基因名称1]、[具体基因名称2]、[具体基因名称3]和[具体基因名称4]基因变异与TKI反应和疾病预后的关联。为此，我们通过聚合酶链反应（PCR）对187例CML患者的rs4880（[具体基因名称1]）、rs1050450（[具体基因名称2]）、rs1001179（[具体基因名称3]）、rs6721961、rs4893819、rs35652124、rs6706649、rs13001694（[具体基因名称4]）和rs113540846（[具体基因名称5]）变异进行了基因分型。我们的结果表明，与氧化应激相关的基因变异会影响TKI耐药性的发展和程度（[具体基因名称1]的等位基因G和GG基因型以及rs4893819的[具体基因名称5]的CT基因型）、[具体基因名称6]基因中突变的出现（rs13001694的[具体基因名称4]的AG基因型以及[具体基因名称1]/[具体基因名称5]轴的GGCTTCCCGG基因谱）、疾病进展（[具体基因名称1]的AG基因型以及rs4893819的[具体基因名称5]的CT基因型）以及CML患者的总生存期（[具体基因名称1]的CC基因型以及rs13001694的[具体基因名称4]的GG基因型）。我们的研究发现，氧化应激相关基因的变异会影响CML的治疗反应和预后。
