Abstract
Multiple myeloma (MM) is a plasma cell dyscrasia characterized by bone marrow infiltration of clonal plasma cells. The recent literature has clearly demonstrated clonal heterogeneity in terms of both the genomic and transcriptomic signature of the tumor. Of note, novel studies have also highlighted the importance of the functional cross-talk between the tumor clone and the surrounding bone marrow milieu, as a relevant player of MM pathogenesis. These findings have certainly enhanced our understanding of the underlying mechanisms supporting MM pathogenesis and disease progression. Within the specific field of small non-coding RNA-research, recent studies have provided evidence for considering microRNAs as a crucial regulator of MM biology and, in this context, circulating microRNAs have been shown to potentially contribute to prognostic stratification of MM patients. The present review will summarize the most recent studies within the specific topic of microRNAs and circulating microRNAs in MM.
Highlights
Multiple myeloma (MM) represents the second most common hematological malignancy [1]. It is a B-cell disorder characterized by clonal growth and accumulation of malignant plasma cells (PCs) within the bone marrow (BM), and the presence of a monoclonal immunoglobulin in the serum and/or urine [2,3,4]
The growth of clonal cells within the marrow: (i) Disrupts the equilibrium between bone-forming osteoblasts’ and bone-resorbing osteoclasts’ activity, which is crucial in the metabolism and turnover of bone tissues; and (ii) triggers inflammatory cytokines, such as interleukin-3 (IL-3), interleukin-6 (IL-6), and macrophage inflammatory proteins-1α (MIP-1α) as well as the receptor activator of nuclear factor-kB ligand (RANK-L), promoting osteoclast activation [5,6]
MicroRNAs have gained attention within the field of MM research due to their pivotal role in the regulation of several cellular processes implicated in plasma cell development and in myelomagenesis [25]
Summary
Multiple myeloma (MM) represents the second most common hematological malignancy [1]. The intermediate stage between MGUS and MM is the smoldering MM (SMM), characterized by a 10% to 60% presence of clonal BM PCs, and serum or urinary M protein with levels ≥30 g/dL and ≥500 mg, respectively At this stage, patients do not present with myeloma-defining events or amyloidosis [7,8]. Interphase fluorescence in situ hybridization (iFISH) revealed that the presence of deletion 17p [del(17p)] or translocation t(4;14), and t(14;16) was associated with a median overall survival of 24.5 months compared to a median overall survival of 50.5 months for patients lacking genetic alterations [19] Another biomarker in MM is the serum lactate dehydrogenase (LDH), of which levels above the upper limit of normal indicate an increased disease aggressiveness [20]. Additional biomarkers are needed to further stratify patients and improve response to therapy
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