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Multiple myeloma is characterized by a clonal expansion of terminally differentiated plasma cells that reside at multiple sites in the bone marrow where they interact with different cell types of the bone marrow micro-environment. The clinical picture is heterogeneous and many of the past and present research efforts have aimed at identifying the underlying factors for this diversity. Furthermore, clinical outcome differs dramatically with a median overall survival (OS) of less than two years for a group of ultra-high risk patients in contrast to patients that achieve durable remissions for many years. Novel treatment approaches have significantly improved survival and intensively treated patients now have an overall median survival between five and nine years. However, myeloma still remains an incurable disease with frequent relapses and development of drug resistance occurring in virtually every patient.
Despite the heterogeneity in disease biology, treatment decisions today are made on the basis of age and performance status rather than individual features of the disease. Understanding the genetics and epigenetics of myeloma should enable us to develop specific therapeutic strategies for individual patients but to achieve this will require the development of robust prognostic and therapeutic biomarkers to identify patient subgroups for study in well-designed clinical trials.