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A highly efficient and faithful MDS patient-derived xenotransplantation model for pre-clinical studies

Author

Listed:
  • Yuanbin Song

    (Yale University School of Medicine)

  • Anthony Rongvaux

    (Yale University School of Medicine
    University of Washington School of Medicine)

  • Ashley Taylor

    (Yale University School of Medicine)

  • Tingting Jiang

    (Yale University School of Medicine)

  • Toma Tebaldi

    (Yale University School of Medicine
    University of Trento)

  • Kunthavai Balasubramanian

    (Yale University School of Medicine)

  • Arun Bagale

    (Yale University School of Medicine
    University of New Haven)

  • Yunus Kasim Terzi

    (Yale University School of Medicine
    Baskent University)

  • Rana Gbyli

    (Yale University School of Medicine)

  • Xiaman Wang

    (Yale University School of Medicine
    The Second Affiliated Hospital of Xi’an Jiaotong University)

  • Xiaoying Fu

    (Yale University School of Medicine
    Shenzhen Children’s Hospital)

  • Yimeng Gao

    (Yale University School of Medicine)

  • Jun Zhao

    (Yale University School of Medicine)

  • Nikolai Podoltsev

    (Yale University School of Medicine)

  • Mina Xu

    (Yale University School of Medicine)

  • Natalia Neparidze

    (Yale University School of Medicine)

  • Ellice Wong

    (VA Medical Center)

  • Richard Torres

    (Yale University School of Medicine)

  • Emanuela M. Bruscia

    (Yale University School of Medicine)

  • Yuval Kluger

    (Yale University School of Medicine
    Yale University
    Yale University)

  • Markus G. Manz

    (University Hospital and University of Zurich)

  • Richard A. Flavell

    (Yale University School of Medicine
    Yale University)

  • Stephanie Halene

    (Yale University School of Medicine)

Abstract

Comprehensive preclinical studies of Myelodysplastic Syndromes (MDS) have been elusive due to limited ability of MDS stem cells to engraft current immunodeficient murine hosts. Here we report a MDS patient-derived xenotransplantation model in cytokine-humanized immunodeficient “MISTRG” mice that provides efficient and faithful disease representation across all MDS subtypes. MISTRG MDS patient-derived xenografts (PDX) reproduce patients’ dysplastic morphology with multi-lineage representation, including erythro- and megakaryopoiesis. MISTRG MDS-PDX replicate the original sample’s genetic complexity and can be propagated via serial transplantation. MISTRG MDS-PDX demonstrate the cytotoxic and differentiation potential of targeted therapeutics providing superior readouts of drug mechanism of action and therapeutic efficacy. Physiologic humanization of the hematopoietic stem cell niche proves critical to MDS stem cell propagation and function in vivo. The MISTRG MDS-PDX model opens novel avenues of research and long-awaited opportunities in MDS research.

Suggested Citation

  • Yuanbin Song & Anthony Rongvaux & Ashley Taylor & Tingting Jiang & Toma Tebaldi & Kunthavai Balasubramanian & Arun Bagale & Yunus Kasim Terzi & Rana Gbyli & Xiaman Wang & Xiaoying Fu & Yimeng Gao & Ju, 2019. "A highly efficient and faithful MDS patient-derived xenotransplantation model for pre-clinical studies," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-018-08166-x
    DOI: 10.1038/s41467-018-08166-x
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    Cited by:

    1. Peter Truong & Sylvie Shen & Swapna Joshi & Md Imtiazul Islam & Ling Zhong & Mark J. Raftery & Ali Afrasiabi & Hamid Alinejad-Rokny & Mary Nguyen & Xiaoheng Zou & Golam Sarower Bhuyan & Chowdhury H. S, 2024. "TOPORS E3 ligase mediates resistance to hypomethylating agent cytotoxicity in acute myeloid leukemia cells," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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