Journal of Bone Oncology (Dec 2019)

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

  • 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. Rosol

Journal volume & issue
Vol. 19

Abstract

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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. Keywords: HTLV-1, Lymphoma, Mouse model, Metastasis, Bone resorption