A novel cytological model of B-cell/macrophage biphenotypic cell hodgkin lymphoma in ganp-transgenic mice

Yasuhiro Sakai, Andri Rezano, Seiji Okada, Takahiro Ohtsuki, Yoshiaki Kawashima, Tetsuya Tsukamoto, Motoshi Suzuki, Michinori Kohara, Motohiro Takeya, Nobuo Sakaguchi, Kazuhiko Kuwahara

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Abstract

Hodgkin lymphoma (HL) is one of the most difficult neoplasms in terms of cytopathological research owing to the lack of established cytological murine models. Although HL is believed to be of lymphoid germinal center B-cell origin, HL cells exhibit unique biphenotypic characteristics of B cells and macrophages. B-cell/macrophage biphenotypic cells have also been identified in the spleen of Lyn-deficient mice. Moreover, Lyn-targeting germinal center-associated nuclear protein (GANP)-transgenic mice (Ig-ganpTg mice) spontaneously develop a lymphoid tumor. We aimed to investigate whether the lymphoid tumor developed in Ig-ganpTg mice exhibit biphenotypic characteristics of B cells/macrophages that correspond to human HL. Here, we demonstrated GANP overexpression in human HL cells and found that it may regulate transdifferentiation between B cells and macrophages. We also demonstrated that tumors were comparable with B-cell/macrophage biphenotypic Hodgkinoid lymphomas. The tumor cells expressed macrophage-related F4/80, CD68, and CD204 as well as cytoplasmic B220 and μ-/κ-chains; in addition, these cells exhibited phagocytic activity. These cells also expressed transcripts of CD30; c-fms; and the cytokines monocyte chemoattractant protein (MCP)-1, MCP-5, RANTES, tumor necrosis factor-α and thrombopoietin associated with macrophages as well as granulocyte/macrophage colony-stimulating factor, interleukin (IL)-4, IL-10, IL-12, and IL-13. Ig-ganpTg mice represent a novel cytological model for the study of cytopathological etiology and oncogenesis of HL.

Original languageEnglish
Article number204
JournalCancers
Volume12
Issue number1
DOIs
Publication statusPublished - 01-2020

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All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Sakai, Y., Rezano, A., Okada, S., Ohtsuki, T., Kawashima, Y., Tsukamoto, T., Suzuki, M., Kohara, M., Takeya, M., Sakaguchi, N., & Kuwahara, K. (2020). A novel cytological model of B-cell/macrophage biphenotypic cell hodgkin lymphoma in ganp-transgenic mice. Cancers, 12(1), [204]. https://doi.org/10.3390/cancers12010204