Integrated microRNA analysis of B-cell precursor acute lymphoblastic leukemia

Abstract

Integrated genomic and transcriptome analyses have been carried out to identify molecular diversity in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Despite refined risk classification, patients classified as at a low risk at diagnosis still account for most cases with relapses. Therefore, novel strategies are needed to identify patients with high risk for relapse. MicroRNAs (miRNAs) are non-coding RNAs that bind to mRNAs and regulate the expression levels of their gene products. Although an increasing number of studies have identified miRNAs as potential biomarkers and therapeutic targets in several cancers, there are only a few studies on integrated analysis of miRNA profiling in pediatric BCP-ALL. To comprehensively investigate miRNA and mRNA profiling in pediatric BCP-ALL, we analyzed 140 high-risk patients. Consensus clustering of miRNA expression data identified a distinct profile characterized by global downregulation of miRNAs (miR-low cluster; MLC), and the profile was not associated with any known genetic subgroups. Patients clustered in MLC had worse prognosis, even in hyperdiploid cases. Moreover, a subset of non-MLC samples at diagnosis acquired an MLC-like miRNA profile at relapse. Integrative miRNA:mRNA analysis findings suggest that the downregulation of miRNAs in MLC led to the upregulation of genes of oncogenic signaling pathways. These findings underscore the importance of integrative analysis of miRNA and mRNA and suggest that miRNA-based classification would be helpful for better risk stratification and may improve the outcome in pediatric BCP-ALL.