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Graphdiyne oxide nanosheets display selective anti-leukemia efficacy against DNMT3A-mutant AML cells

Author

Listed:
  • Qiwei Wang

    (Zhejiang University School of Medicine
    Zhejiang University Medical Center
    Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy)

  • Ying Liu

    (National Center for Nanoscience and Technology of China
    University of Chinese Academy of Sciences
    The GBA National Institute for Nanotechnology Innovation)

  • Hui Wang

    (University of Chinese Academy of Sciences
    National Center for Nanoscience and Technology)

  • Penglei Jiang

    (Zhejiang University School of Medicine
    Zhejiang University Medical Center
    Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy)

  • Wenchang Qian

    (Zhejiang University School of Medicine
    Zhejiang University Medical Center
    Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy)

  • Min You

    (National Center for Nanoscience and Technology of China
    University of Chinese Academy of Sciences
    The GBA National Institute for Nanotechnology Innovation)

  • Yingli Han

    (Zhejiang University School of Medicine
    Zhejiang University Medical Center
    Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy)

  • Xin Zeng

    (Zhejiang University School of Medicine
    Zhejiang University Medical Center
    Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy)

  • Jinxin Li

    (Zhejiang University School of Medicine
    Zhejiang University Medical Center
    Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy)

  • Huan Lu

    (Zhejiang University School of Medicine
    Zhejiang University Medical Center
    Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy)

  • Lingli Jiang

    (Zhejiang University School of Medicine
    Zhejiang University Medical Center
    Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy)

  • Meng Zhu

    (Zhejiang University School of Medicine
    Zhejiang University Medical Center
    Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy)

  • Shilin Li

    (National Center for Nanoscience and Technology of China
    University of Chinese Academy of Sciences
    The GBA National Institute for Nanotechnology Innovation)

  • Kang Huang

    (University of Chinese Academy of Sciences
    National Center for Nanoscience and Technology)

  • Mingmin Tang

    (Zhejiang University City College School of Medicine
    Zhejiang University School of Brain Science and Brain Medicine)

  • Xinlian Wang

    (National Center for Nanoscience and Technology of China
    University of Chinese Academy of Sciences
    The GBA National Institute for Nanotechnology Innovation)

  • Liang Yan

    (University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Zecheng Xiong

    (University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Xinghua Shi

    (University of Chinese Academy of Sciences
    National Center for Nanoscience and Technology)

  • Ge Bai

    (Zhejiang University School of Brain Science and Brain Medicine)

  • Huibiao Liu

    (Chinese Academy of Sciences)

  • Yuliang Li

    (Chinese Academy of Sciences)

  • Yuliang Zhao

    (National Center for Nanoscience and Technology of China
    University of Chinese Academy of Sciences)

  • Chunying Chen

    (National Center for Nanoscience and Technology of China
    University of Chinese Academy of Sciences)

  • Pengxu Qian

    (Zhejiang University School of Medicine
    Zhejiang University Medical Center
    Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy)

Abstract

DNA methyltransferase 3 A (DNMT3A) is the most frequently mutated gene in acute myeloid leukemia (AML). Although chemotherapy agents have improved outcomes for DNMT3A-mutant AML patients, there is still no targeted therapy highlighting the need for further study of how DNMT3A mutations affect AML phenotype. Here, we demonstrate that cell adhesion-related genes are predominantly enriched in DNMT3A-mutant AML cells and identify that graphdiyne oxide (GDYO) display an anti-leukemia effect specifically against these mutated cells. Mechanistically, GDYO directly interacts with integrin β2 (ITGB2) and c-type mannose receptor (MRC2), which facilitate the attachment and cellular uptake of GDYO. Furthermore, GDYO binds to actin and prevents actin polymerization, thus disrupting the actin cytoskeleton and eventually leading to cell apoptosis. Finally, we validate the in vivo safety and therapeutic potential of GDYO against DNMT3A-mutant AML cells. Collectively, these findings demonstrate that GDYO is an efficient and specific drug candidate against DNMT3A-mutant AML.

Suggested Citation

  • Qiwei Wang & Ying Liu & Hui Wang & Penglei Jiang & Wenchang Qian & Min You & Yingli Han & Xin Zeng & Jinxin Li & Huan Lu & Lingli Jiang & Meng Zhu & Shilin Li & Kang Huang & Mingmin Tang & Xinlian Wan, 2022. "Graphdiyne oxide nanosheets display selective anti-leukemia efficacy against DNMT3A-mutant AML cells," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33410-w
    DOI: 10.1038/s41467-022-33410-w
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    References listed on IDEAS

    as
    1. Lê, Sébastien & Josse, Julie & Husson, François, 2008. "FactoMineR: An R Package for Multivariate Analysis," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 25(i01).
    2. Mahmoud Ghandi & Franklin W. Huang & Judit Jané-Valbuena & Gregory V. Kryukov & Christopher C. Lo & E. Robert McDonald & Jordi Barretina & Ellen T. Gelfand & Craig M. Bielski & Haoxin Li & Kevin Hu & , 2019. "Next-generation characterization of the Cancer Cell Line Encyclopedia," Nature, Nature, vol. 569(7757), pages 503-508, May.
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