Comprehensive miRNA expression profiling in human T-cell acute lymphoblastic leukemia by small RNA-sequencing

Abstract

Abstract T-cell acute lymphoblastic leukemia (T-ALL) is a genetically heterogeneous disease that can be classified into different molecular genetic subtypes according to their mRNA gene expression profile. In this study, we applied RNA sequencing to investigate the full spectrum of miRNA expression in primary T-ALL patient samples, T-ALL leukemia cell lines and healthy donor thymocytes. Notably, this analysis revealed that genetic subtypes of human T-ALL also display unique miRNA expression signatures, which are largely conserved in human T-ALL cell lines with corresponding genetic background. Furthermore, small RNA-sequencing also unraveled the variety of isoforms that are expressed for each miRNA in T-ALL and showed that a significant number of miRNAs are actually represented by an alternative isomiR. Finally, comparison of CD34+ and CD4+CD8+ healthy donor thymocytes and T-ALL miRNA profiles allowed identifying several novel miRNAs with putative oncogenic or tumor suppressor functions in T-ALL. Altogether, this study provides a comprehensive overview of miRNA expression in normal and malignant T-cells and sets the stage for functional evaluation of novel miRNAs in T-ALL disease biology.