Mouse Model Recapitulates the Phenotypic Heterogeneity of Human Adult T-cell Leukemia/Lymphoma in Bone

Publication date: Available online 20 August 2019Source: Journal of Bone OncologyAuthor(s): Nicole A. Kohart, Said M. Elshafae, Wachirapan Supsahvad, Aylin Alasonyalilar-Demirer, Amanda R. Panfil, Jingyu Xiang, Wessel P. Dirksen, Deborah J. Veis, Patrick L. Green, Katherine N. Weilbaecher, Thomas J. RosolAbstractAdult 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 mini...
Source: Journal of Bone Oncology - Category: Cancer & Oncology Source Type: research