High miR‐202‐5p Expression at Initial Diagnosis is Associated With Tyrosine Kinase Inhibitor Resistance In Chronic Myeloid Leukemia—A Result From a Nested Case‐Control Study

TL;DR

High levels of miR-202-5p at diagnosis are linked to resistance to tyrosine kinase inhibitors in chronic myeloid leukemia patients.

Contribution

This study validates miR-202-5p as a potential biomarker for predicting TKI resistance in CML at initial diagnosis.

Findings

miR-202-5p expression was significantly higher in TKI-resistant CML patients compared to sensitive patients.

Elevated miR-202-5p levels were strongly correlated with increased risk of TKI resistance (OR = 15.21).

miR-202-5p showed moderate accuracy in predicting TKI resistance (AUC = 0.73).

Abstract

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

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