The mechanisms of bone lesions in human plasmacytomas.
Bone involvement, mainly bone destruction, is a characteristic feature of human plasma-cytomas (PCT); on the other hand, it is exceptional in B cell malignancies other than PCT. Bone destruction is the consequence of an uncoupling process (associating an increased osteoclastic resorption with an inhibition of bone formation) and of a marked bone loss. Conversely, patients lacking lytic bone lesions or those with sclerotic PCT have an increased bone resorption but maintain a normal or have an increased bone formation (coupling process). This excessive osteoclastic resorption is an early phenomenon, as opposed to the inhibition of bone formation, and is observed several months or years before the occurrence of the first clinical symptoms of the disease. Thus, it is an early criterion of malignancy, useful for discriminating benign monoclonal gammopathy and smoldering PCT from early active PCT. Several inflammatory cytokines, osteoclast colony-stimulating factors and osteoclast activating factors produced either by the PCT cells themselves or the hematopoietic microenvironment, are probably involved in the pathogenesis of such bone lesions. At the present time, interleukin 6 (IL-6), (a major PCT-cell growth factor), its agonistic receptor gp80, IL-1 beta and tumor necrosis factor-alpha appear to be the most critical factors. Indirect arguments suggest that other hematopoietic growth factors, mainly macrophage colony-stimulating factor, might play a role. Taken together, these data demonstrate a close relationship between PCT-cell growth factors and factors involved in the occurrence of bone lesions.
Bataille
R
R
Laboratoire d'Hématologie, Institut de Biologie, quai Moncousu, France.
D000818:Animals; D016723:Bone Remodeling / Q000502:physiology; D001862:Bone Resorption / Q000473:pathology / Q000503:physiopathology; D001842:Bone and Bones / Q000473:pathology*; D016207:Cytokines / Q000502:physiology; D016298:Hematopoietic Cell Growth Factors / Q000502:physiology; D006801:Humans; D010006:Osteoblasts / Q000473:pathology / Q000502:physiology; D010010:Osteoclasts / Q000473:pathology / Q000502:physiology; D010950:Plasma Cells / Q000473:pathology / Q000502:physiology; D010954:Plasmacytoma / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology
D016207:Cytokines; D016298:Hematopoietic Cell Growth Factors