Osteopontin dysregulation and lytic bone lesions in multiple myeloma

Osteopontin (OPN), a secreted phosphoprotein involved in immune regulation and bone homeostasis, is a major component of bone, the natural habitat of long-lived plasma cells and multiple myeloma (MM). We show that only some MM cell lines and primary patient samples express OPN at high levels. High OPN expression inversely correlates with bone disease. When we subdivide MM into molecular subtypes, OPN is significantly upregulated in patients with maf translocations, particularly in the fraction lacking bone disease. OPN is produced in osteolytic lesions: we propose that MM-derived OPN plays a critical role in bone disease by protecting bone from destruction.