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Open AccessArticle

A Novel Cytological Model of B-Cell/Macrophage Biphenotypic Cell Hodgkin Lymphoma in Ganp-Transgenic Mice

1
Department of Diagnostic Pathology, Fujita Health University School of Medicine, Aichi 470-1192, Japan
2
Department of Biomedical Sciences, Division of Cell Biology, Faculty of Medicine, Universitas Padjadjaran, West Java 45363, Indonesia
3
Division of Hematopoiesis, Joint Research Center for Retroviral Infection, Kumamoto University, Kumamoto 860-0811, Japan
4
Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan
5
Department of Molecular Oncology, Fujita Health University School of Medicine, Aichi 470-1192, Japan
6
Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan
7
Department of Immunology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan
*
Author to whom correspondence should be addressed.
These authors are contributed equally to this work.
Cancers 2020, 12(1), 204; https://doi.org/10.3390/cancers12010204
Received: 30 November 2019 / Revised: 9 January 2020 / Accepted: 11 January 2020 / Published: 14 January 2020
(This article belongs to the Special Issue Cytologic Features of Tumor)
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. View Full-Text
Keywords: B-cell/macrophage biphenotypic cell; germinal center; germinal center-associated nuclear protein; Hodgkin lymphoma B-cell/macrophage biphenotypic cell; germinal center; germinal center-associated nuclear protein; Hodgkin lymphoma
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Sakai, Y.; Rezano, A.; Okada, S.; Ohtsuki, T.; Kawashima, Y.; Tsukamoto, T.; Suzuki, M.; Kohara, M.; Takeya, M.; Sakaguchi, N.; Kuwahara, K. A Novel Cytological Model of B-Cell/Macrophage Biphenotypic Cell Hodgkin Lymphoma in Ganp-Transgenic Mice. Cancers 2020, 12, 204.

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