Pathogenesis of multiple myeloma

Multiple myeloma (MM) is monoclonal tumor of antibody secreting plasma cells (PC) in the bone marrow (BM), that is often diagnosed by the presence of a typical M-spike by serum protein electrophoresis (SPEP), or by free light chains in the urine. Its symptomatic phase is associated with significant end organ damage including lytic bone lesions, anemia, loss of kidney function, immunodeficiency, and amyloid deposits in various tissues [1]. MM incidence is higher in blacks than whites, and in men than women [2], for a total estimate of 21,700 cases and 10,710 deaths in the United States in 2012 [3]. Although MM continues to be considered an incurable disease, thanks to the recent therapeutic advances, the 5-year survival rate reported in the SEER database has increased from 28 % (1987–1989) to 43 % (2002–2008) [2]. Notably, a subset of patients with cytogenetically defined low-risk MM, initially treated in 1999 were reported having a 10-year survival rate of 75 % [4], with presumably even better results possible for patients starting treatment today. MM cells are the malignant counterpart of post-germinal center (GC) long-lived PCs, characterized by strong BM dependence, somatic hypermutation (SHM) of immunoglobulin (Ig) genes, and isotype class switch resulting in the absence of IgM expression in all but 1 % of tumors [5]. However, MM cells differ from healthy PCs because they retain the potential for a low rate of proliferation (1–3 % of cycling cells).