{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T13:37:52Z","timestamp":1789911472584,"version":"4.0.1"},"reference-count":31,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2006,12,8]],"date-time":"2006-12-08T00:00:00Z","timestamp":1165536000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2007,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Anti\u2010resorptive bisphosphonates are used for the treatment of hypercalcaemia and bone complications associated with malignancies and osteoporosis, but also have been shown to have anti\u2010tumour effects in various cancers. Adult T\u2010cell leukaemia (ATL) is a fatal T\u2010cell malignancy caused by infection with human T\u2010cell leukaemia virus type I (HTLV\u2010I), and remains incurable. ATL is associated with osteolytic bone lesions and hypercalcaemia, both of which are major factors in the morbidity of ATL. Thus, the search for anti\u2010ATL agents that have both anti\u2010tumour and anti\u2010resorptive activity is warranted. The bisphosphonate agent, incadronate, prevented cell growth of HTLV\u2010I\u2010infected T\u2010cell lines and primary ATL cells, but not of non\u2010infected T\u2010cell lines or normal peripheral blood mononuclear cells. Incadronate induced S\u2010phase cell cycle arrest and apoptosis in HTLV\u2010I\u2010infected T\u2010cell lines, and treatment of these cells with substrates of the mevalonate pathway blocked the incadronate\u2010mediated growth suppression. Incadronate also prevented the prenylation of Rap1A protein. These results demonstrated that incadronate\u2010induced growth suppression occurs by interfering with the mevalonate pathway. Importantly, treatment with incadronate reduced tumour formation from an HTLV\u2010I\u2010infected T\u2010cell line when these cells were inoculated subcutaneously into severe combined immunodeficient mice. These findings suggest that incadronate could be potentially useful for the treatment of ATL.<\/jats:p>","DOI":"10.1111\/j.1365-2141.2006.06445.x","type":"journal-article","created":{"date-parts":[[2006,12,8]],"date-time":"2006-12-08T12:35:39Z","timestamp":1165581339000},"page":"424-432","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Bisphosphonate incadronate inhibits growth of human T\u2010cell leukaemia virus type I\u2010infected T\u2010cell lines and primary adult T\u2010cell leukaemia cells by interfering with the mevalonate 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