Mechanisms of Humoral Hypercalcemia of Malignancy in Leukemia/Lymphoma

Hypercalcemia with multiple osteolytic lesions and increased circulating tumor necrosis factor in an adult patient with B-cell acute lymphoblastic leukemia

“…Proinflammatory cytokines, such as TNF-α, IL-1, Figure 1. Multiple osteolytic lesions in the skull and pelvis (A and B) 1.5 (0.0-3.9 pg/ml) IL-1β <5.0 (0.0-5.0 pg/ml) PTH -parathyroid hormone; TNF-α -tumor necrosis factor alpha; IL -interleukin; H -high; L -low and IL-6 have been shown to play an important role in the pathogenesis of hypercalcemia in malignant disorders [3,13]. These mediators promote bone resorption by activation of osteoclasts via the interaction of receptor activator of nuclear factor-kB (RANK) on osteoclasts with RANK ligand on osteoblasts or stromal cells [13].…”

“…Bone osteolytic lesions and hypercalcemia are rare events in most hematologic malignancies, except in patients with multiple myeloma and in adult T-cell leukemia/lymphoma (ATLL) patients associated with human T-cell leukemia/ lymphoma virus-1 [1,2]. Many bone regulatory factors secreted by cancer cells that activate osteoclasts may induce hypercalcemia and osteolytic lesions [3].…”