Conditions associated with an M-protein. Although MGUS is a premalignant condition, approximately 40% of all MGUS patients are considered low-risk MGUS and have a lifetime risk of progression of only 2%.32 Acquisition of somatic genetic abnormalities in the tumor cells and changes in the BM microenvironment may lead to progression to SMM and MM. SMM includes patients with premalignancy and patients with early asymptomatic malignancy. The clone may produce a protein with altered conformation, which may aggregate improperly, causing progressive organ dysfunction. These conditions include AL amyloidosis, LCDD, and type I cryoglobulinemia. Other conditions, such as type II cryoglobulinemia, chronic cold agglutinin disease, and autoimmune neuropathies, are caused by the autoantibody activity of the M-protein, which in most cases is an IgM. Finally, other rare diseases are associated with monoclonal gammopathies, but their pathogenesis is still unclear. This is the case for POEMS syndrome, scleromyxedema, and Schnitzler syndrome.
