Non-Coding RNAs: The “Dark Side Matter” of the CLL Universe

For many years in the field of onco-hematology much attention has been given to mutations in protein-coding genes or to genetic alterations, including large chromosomal losses or rearrangements. Despite this, biological and clinical needs in this sector remain unmet. Therefore, it is not surprising that recent studies have shifted from coded to non-coded matter. The discovery of non-coding RNAs (ncRNAs) has influenced several aspects related to the treatment of cancer. In particular, in chronic lymphocytic leukemia (CLL) the knowledge of ncRNAs and their contextualization have led to the identification of new biomarkers used to follow the course of the disease, to the anticipation of mechanisms that support resistance and relapse, and to the selection of novel targeted treatment regimens. In this review, we will summarize the main ncRNAs discovered in CLL and the molecular mechanisms by which they are affected and how they influence the development and the progression of the disease.