Plasma-derived exosomal miR-326, a prognostic biomarker and novel candidate for treatment of drug resistant pediatric acute lymphoblastic leukemia

• Published in: Scientific reports Vol. 14; no. 1; p. 691
• Main Authors: Saffari, Neda, Rahgozar, Soheila, Faraji, Elaheh, Sahin, Fikrettin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06.01.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/337; 631/67; 631/80; 692/308; 692/4017; 692/4028; 692/53; Acute lymphoblastic leukemia; Cancer; Cell culture; Cell viability; Drug resistance; Electron microscopy; Exosomes; Fluorescence microscopy; Humanities and Social Sciences; Immunoblotting; Internalization; Leukemia; Lymphatic leukemia; Microscopy; multidisciplinary; Nanoparticles; Patients; Pediatrics; Science; Science (multidisciplinary); Transfection
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-50628-w

Acute lymphoblastic leukemia (ALL) is a cancer with high incidence rate in pediatrics and drug resistance is a major clinical concern for ALL treatment. The current study was designed to evaluate the role of exosomal miR-326 in diagnosis and treatment of children with B-ALL. Exosomes were isolated from plasma samples of 30 patients and B-ALL cell lines followed by characterization, using nanoparticle tracking analysis, immunoblotting assay and electron microscopy. qPCR showed significantly increased levels of miR-326 in patients exosomes compared with non-cancer controls ( P  < 0.05, AUC = 0.7500). Moreover, a comparison between the sensitive and drug resistant patients revealed a prognostic value for the exosomal miR326 ( P  < 0.05, AUC = 0.7755). Co-culture studies on drug resistant patient primary cells and B-ALL cell lines suggested that exosomes with high miR-326 level act as vehicles for reducing cells viability. B-ALL cell line transfection with naked miR-326 mimic confirmed the results, and fluorescence microscopy validated uptake and internalization of exosomes by target cells. The novel introduced features of the exosomal miR-326 address a non-invasive way of diagnosing primary drug resistance in pediatric ALL and advocates a novel therapeutic strategy for this cancer.