Role of the Bone Marrow Milieu in Multiple Myeloma Progression and Therapeutic Resistance

Multiple myeloma (MM) is a cancer of the plasma cells within the bone marrow (BM). Studies have shown that the cellular and noncellular components of the BM milieu, such as cytokines and exosomes, play an integral role in MM pathogenesis and progression by mediating drug resistance and inducing MM proliferation. Moreover, the BM microenvironment of patients with MM facilitates cancer tolerance and immune evasion through the expansion of regulatory immune cells, inhibition of antitumor effector cells, and disruption of the antigen presentation machinery. These are of special relevance, especially in the current era of cancer immunotherapy. An improved understanding of the supportive role of the MM BM microenvironment will allow for the development of future therapies targeting MM in the context of the BM milieu to elicit deeper and more durable responses. In the present review, we have discussed our current understanding of the role of the BM microenvironment in MM progression and resistance to therapy and discuss novel potential approaches to alter its pro-MM function.