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CD30 stimulation induces multinucleation and chromosomal instability in HTLV-1-infected cell lines

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Abstract

A recent report indicated involvement of CD30 in progression of human leukemia virus type 1 (HTLV-1) infection, but the exact roles of CD30 in this process remain unclear. This study was conducted to determine the role of CD30 by stimulating CD30 expressed on HTLV-1-infected cell lines with CD30 ligand and observing its effects. CD30 stimulation increased multinucleated cells and inhibited proliferation of HTLV-1-infected cells. This inhibition was recovered by interruption of CD30 stimulation. Chromatin bridges found in multinucleated cells suggested DNA damage. CD30 stimulation triggered DNA double-strand breaks (DSBs) and chromosomal imbalances. CD30 stimulation induced reactive oxygen species (ROS), which induced DSBs. Generation of ROS and multinucleated cells by CD30 was dependent on phosphoinositide 3-kinase. RNA sequencing showed that CD30 stimulation produced significant changes in gene expression profiles, including upregulation of programmed death ligand 1 (PD-L1). Tax, which has also been shown to induce multinucleation and chromosomal instability, failed to induce CD30. These results suggest that induction of CD30, independent of Tax, triggers morphological abnormalities, chromosomal instability, and alteration of gene expression in HTLV-1-infected cells.

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The data are available from the corresponding author upon reasonable request.

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Acknowledgements

This work was supported in part by MEXT/JSPS KAKENHI grants to R.H. (17K08728 and 20K07379) and M.W. (19K07442). This work was also supported by grants from Kitasato University School of Allied Health Sciences (Grant-in-Aid for Research projects) to R.H. (Nos. 2021-1001 and 2022-1007) and M.W. (No 2022-1047).

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Authors and Affiliations

  1. Division of Hematology, Department of Laboratory Sciences, School of Allied Health Sciences, Kitasato University, 1-15-1 Kitasato, Minami-Ku, Sagamihara, Kanagawa, 252-0373, Japan

    Mariko Watanabe & Ryouichi Horie

  2. Department of Molecular Genetics, School of Medicine, Kitasato University, 1-15-1 Minami-Ku, Kitasato, Sagamihara, Kanagawa, 252-0374, Japan

    Hiromi Hatsuse & Kazuaki Nagao

  3. School of Medicine, University of the Ryukyus, Uehara 207, Nishihara-Cho, Okinawa, 903-0125, Japan

    Yuetsu Tanaka

  4. Laboratory of Practical Management of Medical Information, Graduate School of Medicine, St. Marianna University, 2-16-1 Sugao, Miyamae-Ku, Kawasaki, Kanagawa, 216-8511, Japan

    Toshiki Watanabe

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  1. Mariko Watanabe
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  2. Hiromi Hatsuse
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  3. Kazuaki Nagao
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  4. Yuetsu Tanaka
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  5. Toshiki Watanabe
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  6. Ryouichi Horie
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Correspondence to Ryouichi Horie.

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Watanabe, M., Hatsuse, H., Nagao, K. et al. CD30 stimulation induces multinucleation and chromosomal instability in HTLV-1-infected cell lines. Int J Hematol 118, 75–87 (2023). https://doi.org/10.1007/s12185-023-03583-1

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  • DOI: https://doi.org/10.1007/s12185-023-03583-1

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