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FOXM1 regulates leukemia stem cell quiescence and survival in MLL-rearranged AML

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  • Yue Sheng

    (University of Florida
    University of Illinois at Chicago)

  • Chunjie Yu

    (University of Florida
    University of Illinois at Chicago)

  • Yin Liu

    (University of Florida
    University of Illinois at Chicago)

  • Chao Hu

    (University of Illinois at Chicago)

  • Rui Ma

    (University of Illinois at Chicago)

  • Xinyan Lu

    (Feinberg School of Medicine)

  • Peng Ji

    (Feinberg School of Medicine)

  • Jianjun Chen

    (Department of System Biology)

  • Benjamin Mizukawa

    (Cancer & Blood Diseases Institute, Cincinnati Children’s Hospital Medical Center)

  • Yong Huang

    (University of Virginia)

  • Jonathan D. Licht

    (University of Florida)

  • Zhijian Qian

    (University of Florida
    University of Illinois at Chicago)

Abstract

FOXM1, a known transcription factor, promotes cell proliferation in a variety of cancer cells. Here we show that Foxm1 is required for survival, quiescence and self-renewal of MLL-AF9 (MA9)-transformed leukemia stem cells (LSCs) in vivo. Mechanistically, Foxm1 upregulation activates the Wnt/β-catenin signaling pathways by directly binding to β-catenin and stabilizing β-catenin protein through inhibiting its degradation, thereby preserving LSC quiescence, and promoting LSC self-renewal in MLL-rearranged AML. More importantly, inhibition of FOXM1 markedly suppresses leukemogenic potential and induces apoptosis of primary LSCs from MLL-rearranged AML patients in vitro and in vivo in xenograft mice. Thus, our study shows a critical role and mechanisms of Foxm1 in MA9-LSCs, and indicates that FOXM1 is a potential therapeutic target for selectively eliminating LSCs in MLL-rearranged AML.

Suggested Citation

  • Yue Sheng & Chunjie Yu & Yin Liu & Chao Hu & Rui Ma & Xinyan Lu & Peng Ji & Jianjun Chen & Benjamin Mizukawa & Yong Huang & Jonathan D. Licht & Zhijian Qian, 2020. "FOXM1 regulates leukemia stem cell quiescence and survival in MLL-rearranged AML," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14590-9
    DOI: 10.1038/s41467-020-14590-9
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    Cited by:

    1. Hue M. La & Jinyue Liao & Julien M. D. Legrand & Fernando J. Rossello & Ai-Leen Chan & Vijesh Vaghjiani & Jason E. Cain & Antonella Papa & Tin Lap Lee & Robin M. Hobbs, 2022. "Distinctive molecular features of regenerative stem cells in the damaged male germline," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Sophie G. Kellaway & Sandeep Potluri & Peter Keane & Helen J. Blair & Luke Ames & Alice Worker & Paulynn S. Chin & Anetta Ptasinska & Polina K. Derevyanko & Assunta Adamo & Daniel J. L. Coleman & Naee, 2024. "Leukemic stem cells activate lineage inappropriate signalling pathways to promote their growth," Nature Communications, Nature, vol. 15(1), pages 1-22, December.

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