Pathogenesis and progression of monoclonal gammopathy of undetermined significance

Abstract

In Caucasians, monoclonal gammopathy of undetermined significance (MGUS) is an age-related condition with prevalence as high as 3% in persons older than 50 years. Compared with whites, blacks have around two- and threefold higher prevalence rates of MGUS and multiple myeloma (MM), respectively. Risk of progression from MGUS to MM has been found to be very similar in whites and blacks. On average, the transformation rate to a malignant monoclonal gammopathy is 1% per year, with the mechanisms of progression likely related to bone marrow microenvironment and/or the cytokine network. Overall, the actuarial probability of progression at 25 years of follow-up is about 30%. However, when the competing causes of death are taken into account, the actual rate of progression is only 11%. The predictors of malignant transformation are the plasma cell mass (M-protein size and/or proportion of plasma cell in the bone marrow), IgA isotype, serum free light-chain ratio and 'evolving' type and ratio between phenotypically aberrant and normal bone marrow plasma cells. It is recommended to follow these patients, particularly those with high risk of progression, annually to detect MM before complications, such as renal failure or extensive skeletal, involvement occur.