Increased Expression of miR‐326 Mediates Chemosensitivity in Pediatric Acute Lymphoblastic Leukemia Through <i>ABCA2</i> and <i>YY1</i> Downregulation: An Observational and Experimental Study

ABSTRACT Background and Aims Multidrug resistance (MDR) is a major determinant of relapse‐associated mortality in pediatric acute lymphoblastic leukemia (pALL). Although miR‐326 downregulation has been associated with poor prognosis, its role in chemoresistance remains undefined. This study investigated the mechanistic contribution of miR‐326 to MDR in pALL. Methods miR‐326 expression was quantified by RT‐qPCR in 58 fresh bone marrow samples and 14 paired diagnosis–relapse slides from pALL patients. A multidrug‐resistant CD10 − CD34 − B‐cell acute lymphoblastic leukemia (B‐ALL) cell line was transfected with miR‐326 mimic, and drug sensitivity was assessed by MTT assay. Bioinformatic analyses identified ABCA2 and YY1 as potential targets of miR‐326, which were validated by RT‐qPCR, Western blotting, and dual‐luciferase reporter assays. Results Low miR‐326 expression was associated with relapse and reduced 4‐year disease‐free survival. Restoration of miR‐326 expression enhanced chemosensitivity and downregulated ABCA2 and YY1 at both mRNA and protein levels. Reporter assays confirmed direct targeting of both genes. Conclusion miR‐326 attenuates MDR in pALL through direct suppression of ABCA2 and YY1, highlighting its potential as a therapeutic target for overcoming chemoresistance in pediatric B‐ALL.