Unraveling the biology of multiple myeloma disease: cancer stem cells, acquired intracellular changes and interactions with the surrounding micro-environment.

Cancerogenesis is believed to be a multistep process composed of different alterations that drive the transformation of normal human cells into highly malignant derivatives. These changes include self-sufficiency in growth signals, insensitivity to growth-inhibitory signals, the evasion of programmed cell death, a limitless replicative potential, sustained angiogenesis, and tissue invasion and metastasis. Some evidence suggests that these cancer cells are derived from immature, proliferative precursors that feed the cancer cell compartment. Both, precursors and cancer cells, intensively interact with their surroundings, commonly described as their micro-environment. The processes above are also important in the biology of multiple myeloma, a malignant bone marrow disorder consisting of monoclonal plasma cells accumulation. In the current review we describe the biology of this disease, stressing the origin of myeloma cells, their acquired genetic changes and interactions with their bone marrow microenvironment.