The multiple myeloma bone eco-system and its relation to oncogenesis

Pure lytic bone lesions are the hallmark of myeloma (MM). MM is the only hematological malignancy associated with lytic bone lesions and the mechanisms of bone destruction are well documented both at the cellular and molecular levels. An uncoupling bone process characterizes MM, with stimulation of bone resorption and inhibition of bone formation. The capacity of MM cells to directly or indirectly inhibit bone formation is specific of MM, although many carcinomas have the capacity to stimulate bone resorption, directly or indirectly in a similar way to MM. Few MM do not develop bone lesions, while true sclerotic MM remain exceptional. Inhibition of bone formation is the major event explaining the transition from MGUS to overt MM. It is now well documented that bone cells regulate MM cell growth, osteoclast stimulating MM cell growth and osteoblasts inhibiting it. Progression of MM from MGUS is characterized by the selection of MM clones able to inhibit osteoblasts, favoring tumor growth. These data underline the interest of new treatments able to regenerate bone.