Ability of myeloma cells to secrete macrophage inflammatory protein (MIP)‐1α and MIP‐1β correlates with lytic bone lesions in patients with multiple myeloma

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Abstract
Macrophage inflammatory protein (MIP)‐1α and MIP‐1β have been identified as candidates for multiple myeloma (MM)‐derived bone‐resorbing factors. To validate the clinical relevance of these observations, we investigated correlations between the ability of MM cells to secrete these chemokines and the extent of MM bone lesions as well as levels of biochemical bone markers in patients with MM. Patients with multiple bone lesions exhibited higher MIP‐1α and MIP‐1β secretion from MM cells along with elevated urinary deoxypyridinoline (Dpd), without significant elevation of serum bone‐specific alkaline phosphatase (BALP) or osteocalcin compared with those with minimal bone lesions. MIP‐1α and MIP‐1β levels correlated positively with urinary Dpd and serum BALP but not with serum osteocalcin. These results provide further evidence for a causal role of MIP‐1α and MIP‐1β in the development of lytic bone lesions, and suggest that MM cells suppress osteoblastic bone formation to cause an imbalance of bone turnover and development of destructive bone lesions.