Understanding myeloma cancer stem cells

Multiple myeloma (MM) is a neoplasm of mature plasma cells [1], characterized by the accumulation of malignant cells in the bone marrow that are dedicated to the production of a monoclonal immunoglobulin [1]. It is also char­ acterized by osteolytic lesions [2], anemia, hyper­ calcemia and renal failure [3]. MM is responsible for approximately 10% of all hematological can­ cers [4] and its incidence is increasing, in part because of an aging trend in the world popula­ tion. Approximately half of all MM patients are older than 70 years and 20% of them are older than 80 years at diagnosis [5]. A major change in the treatment of MM occurred in the last decade, with the discovery of new therapeutic agents, such as immuno­ modulatory drugs (thalidomide and lenalido­ mide) and proteasome inhibitors (bortezomib) [6]. The use of these drugs, in different combi­ nations, improved the complete response rate in patients eligible for autologous hematopoietic stem cell transplantation, and has contributed to prolong progression­free survival and to improve the quality of life of MM patients [7]. However, after more than 30 years of autologous hematopoietic stem cell transplantation use in MM treatment, this procedure is not consid­ ered curative [2]. Even with multiple approaches and promising therapeutic agents, MM remains an incurable disease [3,8]. Thus, a better under­ standing of the molecular pathogenesis of MM is essential for the development of novel drugs capable of overcoming relapses and improving survival in MM.