Exosomal miRNA expression profiling in patients with imatinib-resistant chronic myeloid leukemia
Chronic myeloid leukemia (CML) is a stem cell-derived malignancy driven by the BCR-ABL oncogene. Imatinib (IM) is a targeted therapy used to treat CML; however, primary resistance and molecular evidence of persistent disease have been observed in some patients. Recent evidence suggests that exosome-derived microRNAs (miRNAs) contribute to drug resistance and may serve as novel biomarkers for cancer diagnosis and drug sensitivity prediction. This study aimed to explore the plasma exosomal miRNA profiles in patients with CML to identify biomarkers associated with IM resistance. Exosomes isolated from the plasma of patients with IM-sensitive and -resistant CML patients were characterized, and exosomal miRNA profiling was conducted using RNA sequencing. Differential expression analysis identified 13 upregulated miRNAs and 21 downregulated miRNAs. Bioinformatics analysis highlighted pathways related to autophagy and PI3K-Akt signaling. Among the upregulated miRNAs, miR-451 and miR-16 were significantly elevated in exosomes from IM-resistant patients compared with those from IM-sensitive patients. Target gene analysis of these miRNAs was performed. Our findings suggest that plasma exosomal miRNAs, particularly miR-451 and miR-16, can serve as potential biomarkers for IM resistance in CML. These results offer new insights into the molecular mechanisms underlying IM resistance and may inform future therapeutic strategies. Overall design: case-control study