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J Bone Oncol. 2019 Aug 20;19:100257. doi: 10.1016/j.jbo.2019.100257. eCollection 2019 Dec.

Mouse model recapitulates the phenotypic heterogeneity of human adult T-cell leukemia/lymphoma in bone.

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Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
Department of Radiology, College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
Department of Pathology, Faculty of Veterinary Medicine, Benha University, Kalyubia 3736, Egypt.
Department of Pathology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok, Thailand.
Department of Pathology, Faculty of Veterinary Medicine, Bursa Uludag University, 16059 Bursa, Turkey.
Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, 225 Irvine Hall, Athens, OH 45701, USA.


Adult T-cell leukemia/lymphoma has a unique relationship to bone including latency in the marrow, and development of bone invasion, osteolytic tumors and humoral hypercalcemia of malignancy. To study these conditions, we established and characterized a novel mouse model of ATL bone metastasis. Patient-derived ATL cell lines including three that do not express HTLV-1 oncoprotein Tax (ATL-ED, RV-ATL, TL-Om1), an in vitro transformed human T-cell line with high Tax expression (HT-1RV), and an HTLV-1 negative T-cell lymphoma (Jurkat) were injected intratibially into NSG mice, and were capable of proliferating and modifying the bone microenvironment. Radiography, μCT, histopathology, immunohistochemistry, plasma calcium concentrations, and qRT-PCR for several tumor-bone signaling mRNAs were performed. Luciferase-positive ATL-ED bone tumors allowed for in vivo imaging and visualization of bone tumor growth and metastasis over time. ATL-ED and HT-1RV cells caused mixed osteolytic/osteoblastic bone tumors, TL-Om1 cells exhibited minimal bone involvement and aggressive local invasion into the adjacent soft tissues, Jurkat cells proliferated within bone marrow and induced minimal bone cell response, and RV-ATL cells caused marked osteolysis. This mouse model revealed important mechanisms of human ATL bone neoplasms and will be useful to investigate biological interactions, potential therapeutic targets, and new bone-targeted agents for the prevention of ATL metastases to bone.


ATL, adult T-cell leukemia/lymphoma; Bone resorption; HHM, humoral hypercalcemia of malignancy; HTLV-1; HTLV-1, Human T-cell leukemia virus type 1; Hbz, HTLV-1 basic zipper protein; Lymphoma; Metastasis; Mouse model; NK, natural killer; NOD, non-obese diabetic; NSG, NOD-scid IL2Rgammanull; SCID, CB17-Prkdcscid; Tax, transcriptional activator from the X region; qRT-PCR, quantitative real-time polymerase chain reaction; μCT, micro-computed tomography

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