Tyrosine Kinase Inhibitor (TKI) drugs have significantly improved chronic myeloid leukemia (CML) outcomes. Neopeptides from CML leukemic cells may induce specific immune responses, crucial for deep molecular remission (DMR) and treatment-free remission (TFR).

Here, Ethiopian CML patients (n=162), were typed for HLA by the next generation sequencing method and the single-nucleotide polymorphism of five cytokines using a PCR-SSP assay.

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, p-value=0.0127 respectively). HLA-DRB4*01:03:01 was associated with favorable outcomes (p-value=0.0058). After assigning values for 'low,' 'intermediate,' and 'high' gene expression of SNPs respective cytokine genes, Kaplan–Meier estimates for relapse-free survival, adjusted for age, treatment duration, and relapse risk among post-TKI patients, indicated that a gene expression ratio above the overall median of TNF-α, IL-6, TGF-β1/IL-10, IFNγ and IL-6/IL-10 TGF-β1 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-SNP, surpassing single-SNP, and HLA allele polymorphism showed promise in predicting CML patient outcomes during TKI treatment, prompting further exploration for their potential utility.

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