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Abstract：
Tyrosine kinase inhibitor (TKI) drugs have significantly improved chronic myeloid leukemia (CML) outcomes. Neopeptides from CML cells may induce specific immune responses, which are crucial for deep molecular (DMR) and treatment-free remission (TFR). In this study of Ethiopian patients with CML (n = 162), the HLA alleles and single-nucleotide polymorphisms of five cytokines revealed significant associations with clinical outcomes. Clinically unfavorable outcomes correlated with HLA alleles A*03:01/02, A*23:17:01, B*57:01/02/03, and HLA-DRB4*01:01 (p-value = 0.0347, p-value = 0.0285, p-value = 0.037, and p-value = 0.0127, respectively), while HLA-DRB4*01:03:01 was associated with favorable outcomes (p-value = 0.0058). After assigning values for the \'low\', \'intermediate\', and \'high\' gene expression of the SNPs\' respective cytokine genes, Kaplan-Meier estimates for relapse-free survival, adjusted for age, treatment duration, and relapse risk among patients after the administration of TKIs, indicated that a gene expression ratio above the overall median of TNF-α, IL-6, and the combination of TGF-β1/IL-10, IFNγ, and IL-6/IL-10 TGF-β1 was correlated with a higher likelihood of treatment failure ((RR: 3.01; 95% CI: 1.1-8.3; p-value = 0.0261) and (RR: 2.4; 95% CI: 1.1-5.2; p-value = 0.022), respectively). Multi-SNPs, surpassing single-SNPs, and HLA allele polymorphisms showed promise in predicting outcomes of patients with CML during TKI treatment, prompting further exploration into their potential utility.
摘要：
酪氨酸激酶抑制剂（TKI）药物可显著改善慢性粒细胞白血病（CML）的预后。来自CML细胞的新肽可以诱导特异性免疫反应，这对于深层分子(DMR)和免治疗缓解(TFR)至关重要。在这项对埃塞俄比亚CML患者（n=162）的研究中，HLA等位基因和5种细胞因子的单核苷酸多态性显示与临床结局显著相关.临床不良结果与HLA等位基因A*03：01/02，A*23：17：01，B*57：01/02/03和HLA-DRB4*01：01相关（分别为p值=0.0347，p值=0.0285，p值=0.037和p值=0.0127），而HLA-DRB4*01:03:01与良好结局相关（p值=0.0058）。为\'低\'赋值后，\'中间\',和SNPs各自细胞因子基因的高基因表达，无复发生存率的Kaplan-Meier估计，根据年龄调整，治疗持续时间,TKIs给药后患者的复发风险，表明基因表达率高于TNF-α的总体中位数，IL-6和TGF-β1/IL-10，IFNγ的组合，和IL-6/IL-10TGF-β1与治疗失败的可能性更高（（RR：3.01;95％CI：1.1-8.3;p值=0.0261）和（RR：2.4;95％CI：1.1-5.2;p值=0.022），分别)。多SNP，超越单SNP，HLA等位基因多态性在预测TKI治疗期间CML患者的预后方面显示出希望，促使进一步探索它们的潜在效用。
