Monoclonal gammopathy of undetermined significance is one of the most common pre-malignant disorders. IgG and IgA monoclonal gammopathy of undetermined significance are precursor conditions of multiple myeloma; light-chain monoclonal gammopathy of undetermined significance of light-chain multiple myeloma; and IgM monoclonal gammopathy of undetermined significance of Waldenström's macroglobulinemia and other lymphoproliferative disorders. Clonal burden, as determined by bone marrow plasma cell percentage or M-protein level, as well as biological characteristics, including heavy chain isotype and light chain production, are helpful in predicting risk of progression of monoclonal gammopathy of undetermined significance to symptomatic disease. Furthermore, alterations in the bone marrow microenvironment of monoclonal gammopathy of undetermined significance patients result in an increased risk of venous and arterial thrombosis, infections, osteoporosis, and bone fractures. In addition, the small clone may occasionally be responsible for severe organ damage through the production of a monoclonal protein that has autoantibody activity or deposits in tissues. These disorders are rare and often require therapy directed at eradication of the underlying plasma cell or lymphoplasmacytic clone. In this review, we provide an overview of the clinical relevance of monoclonal gammopathy of undetermined significance. We also give general recommendations of how to diagnose and manage patients with monoclonal gammopathy of undetermined significance.

Department of Clinical Therapeutics National and Kapodistrian University of Athens School of Medicine Greece

Department of Haemato oncology University Hospital Ostrava and Faculty of Medicine Czech Republic

Department of Hematology Aalborg University Hospital Aalborg Denmark

Department of Hematology and Oncology University of Freiburg Medical Center Germany

Department of hematology at Vejle Hospital Denmark

Department of Hematology Erasmus Medical Center Rotterdam The Netherlands

Department of Hematology Memorial Hospital Istanbul Turkey

Department of Hematology St Olavs Hospital Norwegian University of Science and Technology Trondheim Norway

Department of Hematology University Medical Center Utrecht The Netherlands

Department of Hematology VU University Medical Center Amsterdam The Netherlands

Department of Medicine 1 Wilhelminenspital Wien Austria

Divisione di Ematologia dell'Università di Torino Azienda Ospedaliero Universitaria Città della Salute e della Scienza Turin Italy

Institute of Cancer Research Royal Marsden Hospital London UK

Scientific Direction Centro di Riferimento Oncologico della Basilicata Istituto di Ricovero e Cura a Carattere Scientifico Rionero in Vulture Italy

Universitätsklinik Würzburg Medizinische Klinik und Poliklinik 2 Würzburg Germany

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The spectrum of somatic mutations in monoclonal gammopathy of undetermined significance indicates a less complex genomic landscape than that in multiple myeloma