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Introduction

Monoclonal gammopathy of undetermined significance (MGUS) is a clinically asymptomatic, premalignant condition characterized by the production of a monoclonal immunoglobulin (M protein) by clonal plasma cells.  MGUS typically precedes more severe plasma cell disorders (eg, multiple myeloma) and is often discovered incidentally.

Pathogenesis and risk factors

The pathogenesis of MGUS likely begins with genetic changes (eg, mutations affecting cell cycle regulators [eg, cyclin D1], translocations involving the immunoglobulin heavy chain [IgH] locus) in a plasma cell, leading to clonal proliferation and production of M protein.  The clonal plasma cells comprise <10% of cells in the bone marrow and are generally nonaggressive.  Patients have no evidence of end-organ damage (eg, CRAB features [hyperCalcemia, Renal insufficiency, Anemia, Bone lesions], hyperviscosity, hepatosplenomegaly) characteristic of multiple myeloma.

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