lncRNAs–mRNAs Co–Expression Network Underlying Childhood B–Cell Acute Lymphoblastic Leukaemia: A Pilot Study

SIMPLE SUMMARY: Acute lymphoblastic leukemia (ALL) is one of the most common childhood cancers. The ALL onset involves abnormal proliferation and arrest of differentiation of B or T cell progenitors. Recently, long non–coding RNAs (lncRNAs) gained great interest in the B–ALL leukemogenesis, however, so far few “omic” studies investigate lncRNAs and protein–coding gene networks. In our retrospective study, we conceived an integrated bioinformatic approach, by using NGS platform, to discover lncRNAs strongly correlated with aberrantly expressed protein–coding genes. We provided dysregulated lncRNA–mRNA pairs potentially underlying B–ALL pathogenesis. Diagnosis incidence peak of ALL appears approximatively between 1 and 19 years old. lncRNAs may be of clinical utility as non–invasive biomarker for B–ALL onset or therapy response in support of precision medicine. The identification of lncRNA as key regulators in B–ALL could lead to the identification of the altered pathways able to sustain the leukemic growth. ABSTRACT: Long non–coding RNAs (lncRNAs) are emerging as key gene regulators in the pathogenesis and development of various cancers including B lymphoblastic leukaemia (B–ALL). In this pilot study, we used RNA–Seq transcriptomic data for identifying novel lncRNA–mRNA cooperative pairs involved in childhood B–ALL pathogenesis. We conceived a bioinformatic pipeline based on unsupervised PCA feature extraction approach and stringent statistical criteria to extract potential childhood B–ALL lncRNA signatures. We then constructed a co–expression network of the aberrantly expressed lncRNAs (30) and protein–coding genes (754). We cross–validated our in–silico findings on an independent dataset and assessed the expression levels of the most differentially expressed lncRNAs and their co–expressed mRNAs through ex vivo experiments. Using the guilt–by–association approach, we predicted lncRNA functions based on their perfectly co–expressed mRNAs (Spearman’s correlation) that resulted closely disease–associated. We shed light on 24 key lncRNAs and their co–expressed mRNAs which may play an important role in B–ALL pathogenesis. Our results may be of clinical utility for diagnostic and/or prognostic purposes in paediatric B–ALL management.