{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T13:09:18Z","timestamp":1779196158370,"version":"3.51.4"},"reference-count":67,"publisher":"American Society for Clinical Investigation","issue":"19","funder":[{"name":"NIH","award":["PO1 CA100730"],"award-info":[{"award-number":["PO1 CA100730"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,10,3]]},"abstract":"<jats:p>\n                    Osteolytic bone lesions and hypercalcemia are common, serious complications in adult T cell leukemia\/lymphoma (ATL), an aggressive T cell malignancy associated with human T cell leukemia virus type 1 (HTLV-1) infection. The HTLV-1 viral oncogene HBZ has been implicated in ATL tumorigenesis and bone loss. In this study, we evaluated the role of HBZ on ATL-associated bone destruction using HTLV-1 infection and disease progression mouse models. Humanized mice infected with HTLV-1 developed lymphoproliferative disease and continuous, progressive osteolytic bone lesions. HTLV-1 lacking HBZ displayed only modest delays to lymphoproliferative disease but significantly decreased disease-associated bone loss compared with HTLV-1\u2013infected mice. Gene expression array of acute ATL patient samples demonstrated increased expression of\n                    <jats:italic>RANKL<\/jats:italic>\n                    , a critical regulator of osteoclasts. We found that HBZ regulated RANKL in a c-Fos\u2013dependent manner. Treatment of HTLV-1\u2013infected humanized mice with denosumab, a monoclonal antibody against human RANKL, alleviated bone loss. Using patient-derived xenografts from primary human ATL cells to induce lymphoproliferative disease, we also observed profound tumor-induced bone destruction and increased\n                    <jats:italic>c-Fos<\/jats:italic>\n                    and\n                    <jats:italic>RANKL<\/jats:italic>\n                    gene expression. Together, these data show the critical role of HBZ in driving ATL-associated bone loss through RANKL and identify denosumab as a potential treatment to prevent bone complications in ATL patients.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.128713","type":"journal-article","created":{"date-parts":[[2019,10,2]],"date-time":"2019-10-02T11:00:55Z","timestamp":1570014055000},"source":"Crossref","is-referenced-by-count":15,"title":["HTLV-1 viral oncogene HBZ drives bone destruction in adult T cell leukemia"],"prefix":"10.1172","volume":"4","author":[{"given":"Jingyu","family":"Xiang","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel A.","family":"Rauch","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, 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