Pathogenesis of multiple myeloma

Abstract

Multiple myeloma (MM) is ahematologic malignancy characterized by monoclonal plasma cells infiltrating the bone marrow thereby causing anemia and lytic bone lesions. Despite significant improvement in overall survival, most MM patients inevitably, yet unpredictably, develop refractory disease and MM remains largely incurable. This article describes the stages of progression and presents current insights into the pathogenesis of MM. Discussion of basic conceptional works and most recent scientific publications. Genetic predisposition, inflammation and abnormal immune response are responsible for the pathogenesis of MM. The initiating genomic event occurs during Bcell maturation and clonal plasma cells are disseminated within the bone marrow (BM). This early stage is called monoclonal gammopathy of undetermined significance. The next stage of asymptomatic myeloma, shows aBM infiltration >10%. End organ damage defines symptomatic MM requiring treatment. According to most recent studies MM is characterized by spatial clonal heterogeneity, with aggressive clones frequently being restricted to focal lesions and therefore not being detectable at the iliac crest. Aggressive clones often present with complete inactivation of tumor suppressor genes, such as TP53 and are selected during treatment, which explains the difficulties in treating relapsed MM. The tumor biology determines the progression of MM and underlies the heterogeneous response to treatment, which can be observed despite intensive treatment.