Lift the curtain on long non-coding RNAs in hematological malignancies: Pathogenic elements and potential targets

The Human Genome Project in 2001 has opened the Pandora's box on the complexity of DNA structure and transcriptional regulation. Only a small fraction of the 3 billion bases is part of the protein-coding genes, while approximately 98.5% is represented by non-coding sequences. Besides the classical messenger, ribosomal and transfer RNAs, the "cellular RNA world" is made of short and long non-coding RNAs (lncRNAs) that play regulatory or structural roles, shifting the balance of pathogenic gene variations from coding to non-coding genome. LncRNAs are 200 and 100,000 nucleotide long molecules, not translated into protein, highly heterogeneous in terms of expression within the cells, showing tissue and stage specificity. They are emerging as modifiers of epigenetic, transcription, and translation processes, and can be implicated in the pathogenesis of cancers. In this review, we will focus on B, T and NK hematological malignancies, with the aim of presenting an update on lncRNAs landscape and on their role as potential oncogenes or oncosuppressors. Moreover, we will talk over the bi-directional crosstalk between lncRNAs and epigenetics since these modifications can impact on lncRNAs expression, and, in turn, non-coding transcripts can regulate chromatin organization and transcriptional processes. Finally, we will point the attention on their use as potential biomarkers for diagnostic and prognostic purposes, and possibly as attractive targets in a translational perspective, opening for novel therapeutic options.