MicroRNAs and the diagnosis of childhood acute lymphoblastic leukemia: systematic review, meta-analysis and re-analysis with novel SmallRNA-seq tools

MicroRNAs (miRNAs) have been under the spotlight during the last three decades. These non-coding RNAs appear to be dynamic regulators of mRNA stability and translation, while also interfering with transcription. Circulating miRNAs play a critical role in 19 cell-to-cell interplay, and thus they can serve as disease biomarkers. Meta-analysis of published data revealed that the CC genotype of rs4938723 in pri-miR-34b/c and the TT genotype of rs543412 in miR-100 confer protection against acute lymphoblastic leukemia (ALL) occurrence in children. Re-analysis of smallRNA-seq data with novel tools identified significantly overexpressed members of the miR-128, miR-23, miR-181, miR-130, and miR-17 families and significantly lower expression of the miR-30 family, miR-24-2 and miR-143~145 clusters, miR-574, and miR-618 in pediatric T-ALL cases compared with controls. Inconsistencies in methodology and study designs in most published material preclude reproducibility, and further cohort studies need to be conducted to enable novel tools, such as ALLSorts and RNAseqCNV.