High miR-202-5p Expression at Initial Diagnosis is Associated With Tyrosine Kinase Inhibitor Resistance In Chronic...

Tyrosine kinase inhibitor (TKI) resistance remains a critical challenge in chronic myeloid leukemia (CML). While mechanistic studies implicate miR-202-5p in resistance, its clinical relevance as a biomarker at diagnosis requires validation.

A nested case-control design was employed within a prospective cohort of 797 newly diagnosed chronic-phase CML patients. Of these, 31 patients who developed TKI resistance (per ELN 2020 criteria, without ABL mutations) were matched 1:4 to 124 TKI-sensitive controls on age, sex, Sokal score, and baseline white blood cell count. miR-202-5p expression was quantified by qRT-PCR from diagnostic peripheral blood mononuclear cells (PBMCs). Statistical analyses included conditional logistic regression and receiver operating characteristic (ROC) curve analysis.

The expression level of miR-202-5p was significantly elevated in the TKI-resistant group (1.68 ± 0.45) compared to the TKI-sensitive group (1.26 ± 0.32) (p < 0.001). Conditional logistic regression analysis revealed that elevated miR-202-5p expression was strongly correlated with an increased risk of TKI resistance (OR = 15.21, 95% CI: 4.87-47.51; p < 0.001). ROC curve analysis demonstrated that miR-202-5p had moderate diagnostic accuracy for identifying TKI resistance (AUC = 0.73, 95% CI: 0.65-0.81). Using the optimal cut-off value of 1.63 determined by the Youden Index, the proportion of TKI resistance was significantly higher in the high-expression group (61.29% vs. 12.10%, p < 0.001).

Elevated miR-202-5p expression at diagnosis is significantly associated with TKI resistance in CML. These findings support its potential as a clinical biomarker for identifying high-risk patients, which could aid in early risk stratification and guide therapeutic strategy.

The authors have confirmed clinical trial registration is not needed for this submission.