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Loss of Asxl2 leads to myeloid malignancies in mice

Author

Listed:
  • Jianping Li

    (Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine)

  • Fuhong He

    (Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, Beijing Institute of Genomics, Chinese Academy of Sciences)

  • Peng Zhang

    (Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine)

  • Shi Chen

    (Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine)

  • Hui Shi

    (Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine
    State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Yanling Sun

    (Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, Beijing Institute of Genomics, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Ying Guo

    (Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine)

  • Hui Yang

    (Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine)

  • Na Man

    (Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine)

  • Sarah Greenblatt

    (Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine)

  • Zhaomin Li

    (Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine)

  • Zhengyu Guo

    (and TEES-AgriLife Center for Bioinformatics and Genomic Systems Engineering, Texas A&M University)

  • Yuan Zhou

    (State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Lan Wang

    (Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine)

  • Lluis Morey

    (Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine)

  • Sion Williams

    (Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine)

  • Xi Chen

    (Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine
    University of Miami Miller School of Medicine)

  • Qun-Tian Wang

    (University of Illinois at Chicago)

  • Stephen D. Nimer

    (Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine)

  • Peng Yu

    (and TEES-AgriLife Center for Bioinformatics and Genomic Systems Engineering, Texas A&M University)

  • Qian-Fei Wang

    (Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, Beijing Institute of Genomics, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Mingjiang Xu

    (Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine)

  • Feng-Chun Yang

    (Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine)

Abstract

ASXL2 is frequently mutated in acute myeloid leukaemia patients with t(8;21). However, the roles of ASXL2 in normal haematopoiesis and the pathogenesis of myeloid malignancies remain unknown. Here we show that deletion of Asxl2 in mice leads to the development of myelodysplastic syndrome (MDS)-like disease. Asxl2−/− mice have an increased bone marrow (BM) long-term haematopoietic stem cells (HSCs) and granulocyte–macrophage progenitors compared with wild-type controls. Recipients transplanted with Asxl2−/− and Asxl2+/− BM cells have shortened lifespan due to the development of MDS-like disease or myeloid leukaemia. Paired daughter cell assays demonstrate that Asxl2 loss enhances the self-renewal of HSCs. Deletion of Asxl2 alters the expression of genes critical for HSC self-renewal, differentiation and apoptosis in Lin−cKit+ cells. The altered gene expression is associated with dysregulated H3K27ac and H3K4me1/2. Our study demonstrates that ASXL2 functions as a tumour suppressor to maintain normal HSC function.

Suggested Citation

  • Jianping Li & Fuhong He & Peng Zhang & Shi Chen & Hui Shi & Yanling Sun & Ying Guo & Hui Yang & Na Man & Sarah Greenblatt & Zhaomin Li & Zhengyu Guo & Yuan Zhou & Lan Wang & Lluis Morey & Sion William, 2017. "Loss of Asxl2 leads to myeloid malignancies in mice," Nature Communications, Nature, vol. 8(1), pages 1-14, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15456
    DOI: 10.1038/ncomms15456
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