Abstract
Despite substantial advancements have been done in the understanding of the pathogenesis of plasma cell (PC) disorders, these malignancies remain hard-to-treat. The discovery and subsequent characterization of non-coding transcripts, which include several members with diverse length and mode of action, has unraveled novel mechanisms of gene expression regulation often malfunctioning in cancer. Increasing evidence indicates that such non-coding molecules also feature in the pathobiology of PC dyscrasias, where they are endowed with strong therapeutic and/or prognostic potential. In this review, we aim to summarize the most relevant findings on the biological and clinical features of the non-coding RNA landscape of malignant PCs, with major focus on multiple myeloma. The most relevant classes of non-coding RNAs will be examined, along with the mechanisms accounting for their dysregulation and the recent strategies used for their targeting in PC dyscrasias. It is hoped these insights may lead to clinical applications of non-coding RNA molecules as biomarkers or therapeutic targets/agents in the near future.
Highlights
Plasma cell (PC) dyscrasias represent a clinically and biologically heterogeneous group of blood disorders characterized by the detection of a monoclonal paraprotein in the serum or urine, and/or the presence of monoclonal plasma cell (PC) in the bone marrow (BM) or in extramedullary tissues
A role for the PIWIL–PIWI-interacting RNAs (piRNAs) complex has recently emerged in somatic cells, where their expression can be reactivated under pathological stimuli [33,34]
(d) LncRNAs can modifyby multiple mechanisms: they can mechanisms: act as decoy of transcription factors,ofsponge for miRNAs, ofmiRNAs, splicing, recruiters modifier of complexes or modifier modulate gene expression by multiple they can act as decoy transcription factors,regulators sponge for regulatorsof ofchromatin splicing, recruiters chromatin mRNA
Summary
Plasma cell (PC) dyscrasias represent a clinically and biologically heterogeneous group of blood disorders characterized by the detection of a monoclonal paraprotein in the serum or urine, and/or the presence of monoclonal PCs in the bone marrow (BM) or in extramedullary tissues This set of diseases include monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM), plasma cell leukemia (PCL), lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM), amyloidosis and POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein and Skin changes) syndrome. A pre-malignant condition, defined as IgM MGUS, may precede a clinically active WM It is characterized by less than 10% BM lymphoplasmacytic cells, less than 3g/dL of monoclonal IgM and a lack of clinical signs or symptoms secondary to the WM disease. A role for the PIWIL–piRNA complex has recently emerged in somatic cells, where their expression can be reactivated under pathological stimuli [33,34]
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