Diet-induced obesity promotes a myeloma-like condition in vivo

Multiple myeloma remains a fatal haematological malignancy associated with clonal plasma cell expansion within the bone marrow, osteolytic bone disease, anaemia and renal failure. In almost all cases, myeloma is preceded by the nonmalignant plasma cell disorder monoclonal gammopathy of undetermined significance (MGUS), characterized by an increase in monoclonal immunoglobulin secretion, < 10% plasma cells within the bone marrow and a lack of lytic bone lesions. The mechanisms underlying the pathogenesis of MGUS and progression to myeloma are complex with a major role attributed to the host microenvironment. A loss of host-derived adiponectin is known to promote myeloma development in vivo, both in murine models and in patients with MGUS.(1) Adiponectin is inversely linked to obesity, with increasing epidemiological evidence supporting an association between obesity and MGUS or myeloma.(2-7) In the present study, we have combined a well-characterized murine model of myeloma with diet-induced obesity and a genetic model of obesity to determine the effect of increased obesity on myeloma development in vivo.