Increased Expression of miR-326 Mediates Chemosensitivity in Pediatric Acute Lymphoblastic Leukemia Through ABCA2 and YY1 Downregulation: An Observational and Experimental Study.

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.