microRNA expression profiling of bone marrow and peripheral blood samples in children with B-cell acute lymphoblastic leukemia: MiR-223-3p, miR-363-3p, and miR-708-5p as potential biomarkers

Background: Precursor B-cell acute lymphoblastic leukemia (B-ALL) is the most common subtype of acute lymphoblastic leukemia and the most frequent cancer in pediatric patients. This study aimed to compare microRNA (miRNA) expression profiles between bone marrow and peripheral blood samples and evaluate potential diagnostic biomarkers for childhood B-ALL. Procedure: Peripheral blood and bone marrow samples were collected from children with B-ALL and healthy controls and subjected to miRNA microarray analysis followed by RT-qPCR. Results: Microarray analysis revealed no differences in miRNA expression between peripheral blood and bone marrow samples. Comparison of peripheral blood profiles between B-ALL and control subjects revealed 13 differentially expressed miRNAs. RT-qPCR analysis did not show significant differences between bone marrow and peripheral blood samples for 12 of the 14 miRNAs tested (miR-195-5p,-363-3p,-410-3p,-4701-5p,- 1283p,- 181a-5p,- 181b-5p,- 196b-5p,-708-5p,-222-3p,-125b-5p, and- 223-3p). Furthermore, it was found that miR-410-3p was downregulated and miR-195-5p,-363-3p,-4701-5p,-128-3p,-181a-5p,-181b-5p,-196b-5p,-708-5p,-222-3p, and- 223-3p were upregulated in B-ALL patients. The areas under the curve for miR-223-3p,-363-3p, and- 708-5p were 0.9588 (sensitivity = 85 %, specificity = 100 %), 0.9630 (sensitivity = 89 %, specificity = 100 %), and 0.9794 (sensitivity = 96 %, specificity = 100 %), respectively. Enriched pathway analysis of differentially expressed miRNAs identified genes with important regulatory roles associated with cell cycle, proliferation, and apoptosis. Conclusions: These data suggest an equivalence between peripheral blood and bone marrow miRNA expression profiles and demonstrate the potential of miR-223-3p,-363-3p, and specially- 708-5p as B-ALL biomarkers.