{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T16:41:06Z","timestamp":1772469666749,"version":"3.50.1"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2004,7,1]],"date-time":"2004-07-01T00:00:00Z","timestamp":1088640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Hypercalcemia is observed in &amp;gt;80% of ATL. Serum MIP-1\u03b1 levels were elevated in all 24 ATL with hypercalcemia but undetectable in all 10 patients with humoral hypercalcemia of malignancy with solid tumors and in 34 of 37 ATL without hypercalcemia. We propose that serum MIP-1\u03b1 is a clinical hallmark for hypercalcemia in ATL.<\/jats:p>\n               <jats:p>Introduction: High serum cytokines levels are not always associated with hypercalcemia in patients with adult T-cell leukemia (ATL), suggesting that other factors are involved in the pathogenesis of ATL patients with hypercalcemia. This study was designed to determine the role of macrophage inflammatory protein-1\u03b1 (MIP-1\u03b1), a chemokine recently described as an osteoclast stimulatory factor, in ATL-associated hypercalcemia.<\/jats:p>\n               <jats:p>Materials and Methods: We measured serum interleukin (IL)-1\u03b2, IL-6, TNF-\u03b1, parathyroid hormone-related protein (PTHrP), and MIP-1\u03b1 levels in ATL patients by enzyme-linked immunosorbent assays. FACScan was used to measure the expression of RANKL on ATL cells. Osteoclast formation in cocultures of ATL cells and peripheral blood mononuclear cells (PBMCs) was evaluated by TRACP staining.<\/jats:p>\n               <jats:p>Results: High serum MIP-1\u03b1 levels were noted in all 24 ATL patients with hypercalcemia and in 3 of 37 ATL patients without hypercalcemia. The elevated levels of MIP-1\u03b1 and calcium in ATL patients decreased after effective chemotherapy, emphasizing the role of MIP-1\u03b1 in ATL hypercalcemia. ATL cells spontaneously produced MIP-1\u03b1. MIP-1\u03b1 significantly enhanced human monocyte (precursor cells of osteoclasts) migration and induced RANKL expression on ATL cells. ATL cell-induced osteoclast formation from PBMCs was inhibited by anti-MIP-1\u03b1 antibody and osteoprotegerin.<\/jats:p>\n               <jats:p>Conclusion: Our results suggest that MIP-1\u03b1 can induce RANKL on ATL cells in autocrine fashion and that RANKL seems to mediate the hypercalcemic effect of MIP-1\u03b1 in ATL. We propose that MIP-1\u03b1 is the clinical hallmark of hypercalcemia in ATL and could be a potentially useful therapeutic target.<\/jats:p>","DOI":"10.1359\/jbmr.040314","type":"journal-article","created":{"date-parts":[[2006,4,27]],"date-time":"2006-04-27T00:24:04Z","timestamp":1146097444000},"page":"1105-1111","source":"Crossref","is-referenced-by-count":41,"title":["Macrophage Inflammatory Protein-1\u03b1 Induces Hypercalcemia in Adult T-Cell Leukemia"],"prefix":"10.1093","volume":"19","author":[{"given":"Yosuke","family":"Okada","sequence":"first","affiliation":[{"name":"First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, School of Medicine, Kitakyushu, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junichi","family":"Tsukada","sequence":"additional","affiliation":[{"name":"First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, School of Medicine, Kitakyushu, 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