Expression profiling of microRNAs enriched in small extracellular vesicles isolated from bone marrow plasma of patients with multiple myeloma, extramedullary disease, and plasma cell leukemia
Multiple myeloma is a plasma cell malignancy characterized by the abnormal increase of monoclonal immunoglobulins. Despite great treatment advances, there are still patients experiencing migration of tumor cells from the bone marrow and progression of the disease into its aggressive forms including extramedullary disease or plasma cell leukemia. Although the exact molecular mechanisms are not known, several studies have confirmed the involvement of small extracellular vesicles-enriched microRNAs in multiple myeloma progression. Thus, we have performed the expression profiling of these molecules in bone marrow plasma of patients with multiple myeloma, extramedullary disease, and plasma cell leukemia using next-generation sequencing with the aim to identify new molecules involved in the disease pathogenesis. In total, 42 microRNAs were wound to be significantly deregulated among analyzed subgroups. The independent validation by RT-qPCR confirmed the elevated levels of miR-140-3p, miR-584-5p, miR-191-5p, and miR-143-3p in patients with multiple myeloma compared to extramedullary disease and/or plasma cell leukemia. Subsequent statistical analysis proved several significant correlations between clinical characteristics or flow cytometry parameters of patients and microRNAs' expression. In addition, low levels of miR 140 3p, miR-191-5p, miR-744-5p, and miR-143-3p were associated with worse overall survival. These results indicate that deregulation of microRNAs could contribute to multiple myeloma progression. Nevertheless, the exact mechanisms have yet to be clarified. Overall design: Expression miRNA (isolated from EVs) profile of multiple myeloma, extramedullary disease and plasma cell leukemia patients.