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Myeloma cells express and release RANK-ligand that promotes the generation of osteoclast-like cells


, : Myeloma cells express and release RANK-ligand that promotes the generation of osteoclast-like cells. Blood 98(11 Part 2): 302b, November 16

RANK-ligand (RANKL)/Osteoclast Differentiation Factor has recently been identified as an important cytokine for osteoclast differentiation and activation. We found RANKL to be expressed by plasma cells in 19/19 bone marrow biopsies of myeloma patients and in 8/8 myeloma cell lines. RANKL was primarily located inside the myeloma cells, and was constitutively released to the culture medium of myeloma cell lines. Myeloma cell lines expressed RANKL mRNA. RANKL could not be detected in blood or bone marrow plasma from myeloma patients. It was also found that myeloma-conditioned culture medium together with M-CSF induced the generation of osteoclast-like cells in cultures of human peripheral blood monocytes. This effect was inhibited by osteoprotegerin, the soluble decoy receptor of RANKL. We propose that expression of RANKL by myeloma cells is a significant risk factor for the development of osteolysis in myeloma. Since RANKL was also expressed in plasma cells of myeloma patients with no evidence of osteolytic bone disease other factors such as loss of inhibition of RANKL may be important for the clinical manifestations of expression of RANKL in myeloma. The observation may provide a basis for new strategies for treatment and prevention of osteolysis in myeloma.

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