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Clinicopathological characteristics associated with the engraftment of patient lymphoma cells in NOG mice

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Abstract

Patient-derived xenograft (PDX) mouse models are useful for deepening our understanding of the biology of malignant lymphoma; however, factors associated with the success of the PDX lymphoma model are largely unknown. We retrospectively analyzed the characteristics of 66 xenotransplantations from 65 patients. In all, 43 (65%) specimens were obtained from patients aged > 60 years, and 42 (64%) specimens were obtained at diagnosis. Specimens were obtained from patients with the following diseases: diffuse large B-cell lymphoma (n = 30), intravascular large B-cell lymphoma (n = 12), follicular lymphoma (n = 8), peripheral T-cell lymphoma (n = 7), mantle cell lymphoma (n = 2), and other (n = 7). The specimens were sourced mainly from bone marrow (n = 31, 47%) and extranodal tumors (n = 13, 20%). Engraftment was successful in 33/66 (50%) xenotransplantations. The median age of patients who provided successful specimens was significantly higher than that for unsuccessful specimens (p = 0.013). Specimens with a high proportion of tumor cells in the graft and those obtained from patients with relapsed/refractory disease showed higher tendencies toward successful engraftment. Taken together, these data suggest that tumor cells with a highly malignant potential might have a high likelihood of engraftment.

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Qualified researchers may contact the corresponding author to share further data reported in this article. Request will be reviewed based on scientific merit. In compliance with the domestic ethics guideline, the data including individual deidentified patients’ data underlying the results reported in this article can be shared under the approval of each institutional review board.

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Acknowledgements

We thank Ms. Yoko Matsuyama, Ms. Chika Wakamatsu, Ms. Manami Kira, Ms. Yukie Konishi, Ms. Yuko Kojima, Ms. Saori Kanamori, and Ms. Konomi Ōyama (Nagoya University) for assistance with laboratory work. This work was supported by a JSPS Grant-in-Aid for Young Scientists (B) (No. 14443918) and Grants-in-Aid for Scientific Research (C) (Nos. 17K09922 and 20K08751) to K.S.

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Authors and Affiliations

  1. Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showa-Ku, Nagoya, Aichi, 466-8550, Japan

    Satomi Sahashi, Kazuyuki Shimada, Yusuke Takagi, Tomohiro Aoki, Shunsuke Kunou, Akihiko Sakamoto, Atsushi Murase, Katsuya Furukawa, Yusuke Kagaya, Yusuke Yamaga, Mika Takai, Kiyonobu Tokuyama & Hitoshi Kiyoi

  2. Department of Pathology and Clinical Laboratories, Nagoya University Hospital, Nagoya, Aichi, Japan

    Satoko Shimada & Shigeo Nakamura

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  1. Satomi Sahashi
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Contributions

KS and HK designed the study; SS, KS, YT, TA, SK, AS, AM, KF, YK, YY, MT, and KT performed experiments and collected data; SS, KS, and HK analyzed and interpreted the data; SS and SN evaluated pathological specimens; KS and HK provided financial support; SS and KS performed the statistical analysis; SN and HK supervised the research; and SS, KS, and HK wrote the manuscript. All authors have read and approved the final version of the manuscript.

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Correspondence to Kazuyuki Shimada.

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Conflict of interest

K.S. has received honoraria from AstraZeneca, Eisai, Celgene, Takeda, Janssen, Bristol-Myers Squibb, Chugai, Kyowa Kirin, Nippon Shinyaku, Daiichi Sankyo, Meiji Seika Pharma, Ono, AbbVie, and Novartis; and has received funding from Celgene, Otsuka, and Kyowa Kirin. K.F. has received honoraria from Chugai. H.K. has received research funding from FUJIFILM, Kyowa-Kirin, Bristol-Myers Squibb, Otsuka, Perseus Proteomics, Daiichi Sankyo, AbbVie, CURED, Astellas Pharma, Chugai, Zenyaku Kogyo, Nippon Shinyaku, Eisai, Takeda, Sumitomo Pharma, and Sanofi; and honoraria from AbbVie, Chugai, Astellas Pharma, and Novartis. All other authors have nothing to disclose.

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Sahashi, S., Shimada, K., Takagi, Y. et al. Clinicopathological characteristics associated with the engraftment of patient lymphoma cells in NOG mice. Int J Hematol 118, 221–230 (2023). https://doi.org/10.1007/s12185-023-03604-z

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