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. 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.