Pathogenesis of Monoclonal Gammopathy of Undetermined Significance and Progression to Multiple Myeloma

Monoclonal gammopathy of undetermined significance (MGUS), including immunoglobulin light chain only MGUS, is an age-dependent premalignant tumor that is present in about 4% of Caucasian individuals over the age of 50 years. It is comprised of two different kinds of tumors: about 15% lymphoid or lymphoplasmacytoid MGUS and the remainder plasma cell MGUS. Plasma cell MGUS is stable but can sporadically progress to multiple myeloma (MM) at an average rate of about 1% per year. Most, if not all, MM tumors are preceded by plasma cell MGUS, which shares four partially overlapping oncogenic features with MM. It presently is not possible to unequivocally distinguish an MGUS tumor cell from an MM tumor cell. However, two models based on clinical laboratory tests indicate that it is possible to stratify MGUS tumors into groups that have average rates of progression as low as 0.26% per year and as high as 12% per year.