Medline ® Abstract for Reference 10
of 'Hypercalcemia of malignancy: Mechanisms'
Mechanisms of bone lesions in multiple myeloma and lymphoma.
Cancer. 1997;80(8 Suppl):1557.
BACKGROUND: Bone lesions and hypercalcemia occur rarely in patients with hematologic malignancies, except those patients with multiple myeloma and adult T-cell leukemia/lymphoma (ATL) associated with the human T-cell leukemia/lymphoma virus-1 (HTLV-1) virus. The primary mechanism for bone destruction in patients with myeloma and lymphoma is increased osteoclastic bone resorption. In patients with multiple myeloma, new bone formation is also inhibited. Mediators including lymphotoxin, interleukin-1beta, parathyroid hormone related protein (PTHrP), and interleukin-6, produced by the myeloma cells or by marrow stromal cells in response to myeloma cells, have been implicated as osteoclast-activating factors (OAF) in multiple myeloma. However, most studies to identify OAF produced by myeloma cells have been inconclusive.
METHODS: To try to identify the OAF produced by myeloma cells, we developed an in vivo model of human myeloma bone disease using the ARH-77 myeloma cell line transplanted into severe combined immunodeficiency mice.
RESULTS: We found that a novel cytokine(s) may be responsible for bone destruction. Interleukin-1 and PTHrP mediate bone destruction in patients with ATL. Thesefactors can be detected in media conditioned by ATL cells or by lymphocytes infected with HTLV-1. Furthermore, serum PTHrP levels are increased in ATL patients. In patients with Hodgkin's disease or other types of non-Hodgkin's lymphoma, 1,25-(OH)2D3 or PTHrP is produced by the lymphoma cells and mediates bone destruction. Chemotherapy or resection of the lymphoma decreases 1,25-(OH)2D3 levels and hypercalcemia in these patients.
CONCLUSION: Thus, OAF produced locally by the tumor or the marrow microenvironment play an important role in the bone destruction seen in patients with hematologic malignancies.
Department of Medicine/Hematology, Audie Murphy Veterans Administration Hospital, San Antonio, Texas 78284, USA.