Exosomes in Multiple Myeloma: from bench to bedside.

Multiple myeloma (MM) remains till today an incurable plasma cell malignancy which develops in the bone marrow (BM). This BM is partially responsible for protecting the MM cells against current standard-of-care therapies and for accommodating MM-related symptoms such as bone resorption and immune suppression. Increasing evidence has implicated extracellular vesicles (EV), including exosomes in the different processes within the BM. Exosomes are <150 nm sized vesicles secreted by different cell types including MM cells. These vesicles contain protein and RNA cargo which they deliver to the recipient cell. In this way, they have been implicated in MM-related processes including osteolysis, angiogenesis, immune suppression and drug resistance. Targeting exosome secretion could therefore potentially block these different processes. In this review we will summarize the current findings of exosome-related processes in the BM and describe not only the current treatment strategies to counter them but also how exosomes can be harnessed to deliver toxic payloads. Finally, an overview of the different clinical studies which investigate EV cargo as potential MM biomarkers in liquid biopsies will be discussed.