The emerging role of exosomes in multiple myeloma.

Multiple myeloma (MM), one of the most prevalent hematological malignancies, accounts for approximately 10% of all blood cancers. In spite of the recent advancements in MM therapy, this malignancy of terminally differentiated plasma cells (PCs) continues to remain a hard-to-cure disease due to the emergence of drug resistance and frequent relapses. It is now well-established that the tumor-supportive involvement of the bone marrow microenvironment (BMM) including the cellular and non-cellular elements are the major causes behind treatment failures of MM as well as its main complications such as osteolytic bone loss. Exosomes (EXs) are membranous structures that carry signaling molecules and have recently received a great deal of attention as important mediators of inter-cellular communication in health and disease. EXs involve in the growth and drug resistance of many tumors via delivering their rich contents of bioactive molecules including miRNAs, growth factors, cytokines, signaling molecules, etc. With regard to MM, many studies have reported that EXs are among the main culprits playing key roles in the vicious network within the BMM of these patients. The main producers of EXs that largely contribute to MM pathogenesis are bone marrow stromal cells (BMSCs) as well as MM cells themselves. These cell types produce large amounts of EXs that affect a variety of target cells including natural killer (NK) cells, osteoclasts (OCs) and osteoblasts (OBs) to the advantage of tumor survival and progression. These EXs contain a different profile of proteins and miRNAs from that of EXs obtained from their counterparts in healthy individuals. MM patients exhibit distinguishable elevations in some of their contents such as miR-21, miR-146a, let-7b and miR-18a, while some molecules like miR-15a are markedly downregulated in EXs of MM patients compared to healthy individuals. These findings make EXs desirable biomarkers for early prediction of disease progression and drug resistance in the context of MM. On the other hand, due to the tumor-supportive role of EXs, targeting these structures in parallel to the conventional therapeutic regimens may be a promising approach to a successful anti-MM therapy. In the present work, an extensive review of the literature has been carried out to highlight the recent advances in the field.