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Oncogenic gene expression and epigenetic remodeling of cis-regulatory elements in ASXL1-mutant chronic myelomonocytic leukemia

Author

Listed:
  • Moritz Binder

    (Mayo Clinic
    Mayo Clinic)

  • Ryan M. Carr

    (Mayo Clinic)

  • Terra L. Lasho

    (Mayo Clinic)

  • Christy M. Finke

    (Mayo Clinic)

  • Abhishek A. Mangaonkar

    (Mayo Clinic)

  • Christopher L. Pin

    (University of Western Ontario)

  • Kurt R. Berger

    (University of Western Ontario)

  • Amelia Mazzone

    (Mayo Clinic
    Mayo Clinic)

  • Sandeep Potluri

    (University of Birmingham)

  • Tamas Ordog

    (Mayo Clinic)

  • Keith D. Robertson

    (Mayo Clinic)

  • David L. Marks

    (Mayo Clinic)

  • Martin E. Fernandez-Zapico

    (Mayo Clinic)

  • Alexandre Gaspar-Maia

    (Mayo Clinic
    Mayo Clinic)

  • Mrinal M. Patnaik

    (Mayo Clinic
    Mayo Clinic)

Abstract

Myeloid neoplasms are clonal hematopoietic stem cell disorders driven by the sequential acquisition of recurrent genetic lesions. Truncating mutations in the chromatin remodeler ASXL1 (ASXL1MT) are associated with a high-risk disease phenotype with increased proliferation, epigenetic therapeutic resistance, and poor survival outcomes. We performed a multi-omics interrogation to define gene expression and chromatin remodeling associated with ASXL1MT in chronic myelomonocytic leukemia (CMML). ASXL1MT are associated with a loss of repressive histone methylation and increase in permissive histone methylation and acetylation in promoter regions. ASXL1MT are further associated with de novo accessibility of distal enhancers binding ETS transcription factors, targeting important leukemogenic driver genes. Chromatin remodeling of promoters and enhancers is strongly associated with gene expression and heterogenous among overexpressed genes. These results provide a comprehensive map of the transcriptome and chromatin landscape of ASXL1MT CMML, forming an important framework for the development of novel therapeutic strategies targeting oncogenic cis interactions.

Suggested Citation

  • Moritz Binder & Ryan M. Carr & Terra L. Lasho & Christy M. Finke & Abhishek A. Mangaonkar & Christopher L. Pin & Kurt R. Berger & Amelia Mazzone & Sandeep Potluri & Tamas Ordog & Keith D. Robertson & , 2022. "Oncogenic gene expression and epigenetic remodeling of cis-regulatory elements in ASXL1-mutant chronic myelomonocytic leukemia," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29142-6
    DOI: 10.1038/s41467-022-29142-6
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    References listed on IDEAS

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    1. Groemping, Ulrike, 2006. "Relative Importance for Linear Regression in R: The Package relaimpo," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 17(i01).
    2. Jane Merlevede & Nathalie Droin & Tingting Qin & Kristen Meldi & Kenichi Yoshida & Margot Morabito & Emilie Chautard & Didier Auboeuf & Pierre Fenaux & Thorsten Braun & Raphael Itzykson & Stéphane de , 2016. "Mutation allele burden remains unchanged in chronic myelomonocytic leukaemia responding to hypomethylating agents," Nature Communications, Nature, vol. 7(1), pages 1-13, April.
    3. Antoine Campagne & Ming-Kang Lee & Dina Zielinski & Audrey Michaud & Stéphanie Corre & Florent Dingli & Hong Chen & Lara Z. Shahidian & Ivaylo Vassilev & Nicolas Servant & Damarys Loew & Eric Pasmant , 2019. "BAP1 complex promotes transcription by opposing PRC1-mediated H2A ubiquitylation," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    4. Johanna C. Scheuermann & Andrés Gaytán de Ayala Alonso & Katarzyna Oktaba & Nga Ly-Hartig & Robert K. McGinty & Sven Fraterman & Matthias Wilm & Tom W. Muir & Jürg Müller, 2010. "Histone H2A deubiquitinase activity of the Polycomb repressive complex PR-DUB," Nature, Nature, vol. 465(7295), pages 243-247, May.
    5. Shuhei Asada & Susumu Goyama & Daichi Inoue & Shiori Shikata & Reina Takeda & Tsuyoshi Fukushima & Taishi Yonezawa & Takeshi Fujino & Yasutaka Hayashi & Kimihito Cojin Kawabata & Tomofusa Fukuyama & Y, 2018. "Mutant ASXL1 cooperates with BAP1 to promote myeloid leukaemogenesis," Nature Communications, Nature, vol. 9(1), pages 1-18, December.
    6. Anand Balasubramani & Antti Larjo & Jed A. Bassein & Xing Chang & Ryan B. Hastie & Susan M. Togher & Harri Lähdesmäki & Anjana Rao, 2015. "Cancer-associated ASXL1 mutations may act as gain-of-function mutations of the ASXL1–BAP1 complex," Nature Communications, Nature, vol. 6(1), pages 1-15, November.
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