Bone marrow microenvironment in myelomagenesis: its potential role in early diagnosis

Abstract

Multiple myeloma (MM) is the second most common hematological malignancy, with an overall survival of 4-6 years. It is always preceded by a premalignant stage called monoclonal gammopathy of unknown significance (MGUS). Importantly, at this time we lack reliable predictors to determine who will progress from MGUS to MM, and who will remain stable. The bone marrow microenvironment plays a key role in myelomagenesis (growth, survival and migration of malignant plasma cells). In the present review, we summarize and discuss our current understanding of the bone marrow microenvironment and its compartments in relation to myelomagenesis. Although it remains to be proven, we believe that an improved characterization of the cellular constituents, the extracellular matrix components and the soluble factors of the bone marrow could open up novel avenues to better understand underlying mechanisms of the transformation from MGUS to MM. Ultimately, this will lead to the development of early treatment of high-risk precursor disease aimed to delay/prevent MM.

Figure 1. Microenvironment in myelomagenesis

Note the complexity of the interplay between MM cells and the various microenvironmental cells such as bone marrow stromal cells, osteoblasts, osteoclasts, dendritic cells and endothelial cells. The network of intracellular pathways as a result of release of cytokines and growth factors influences the progression of MGUS to MM. BMSC: Bone marrow stromal cell; MGUS: Monoclonal gammopathy of unknown significance; MM: Multiple myeloma; MMP: Matrix metalloproteinase. Adapted from [135].