Advances in the understanding of IgM monoclonal gammopathy of undetermined significance

Among monoclonal gammopathies of undetermined significance (MGUSs), the immunoglobulin M (IgM) MGUS subtype stands as a unique entity and plays a pivotal role as a pre-malignant condition for multiple B-cell non-Hodgkin lymphomas, most notably Waldenström macroglobulinemia (WM). A relationship between IgM MGUS and WM has been proposed for decades. However, insight regarding the pathobiology of these two conditions improved significantly in recent years, strengthening the hypothesis that WM and IgM MGUS are different stages of the same disease. Therefore, the understanding of IgM MGUS and that of WM are interconnected and advances in one will likely impact the other. Furthermore, IgM MGUS has been more commonly recognized as the underlying etiology of IgM-related disorders. In this review, we explore recent advances in the understanding of the pathobiology of IgM MGUS and WM and the treatment of common IgM-related disorders.