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

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2019-12-01

Authors

Kohart, Nicole A.
Elshafae, Said M.
Supsahvad, Wachirapan
Alasonyalılar-Demirer, Aylin
Panfil, Amanda R.
Xiang Jingyu
Dirksen, Wessel P.
Veis, Deborah J.
Green, Patrick L.
Weilbaecher, Katherine N.

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Elsevier

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Abstract

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-0m1), 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, mu CT, 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-Oml 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.

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Keywords

Hormone-related protein, Leukemia-lymphoma, Humoral hypercalcemia, Gene-expression, Serum-levels, Kappa-b, Mice, Engraftment, Patient, Cancer, Htlv-1, Lymphoma, Mouse model, Metastasis, Bone resorption, Science & technology, Life sciences & biomedicine, Oncology

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