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ZBTB7A mutations in acute myeloid leukaemia with t(8;21) translocation

Author

Listed:
  • Luise Hartmann

    (University Hospital, Ludwig-Maximilians-Universität (LMU) München
    Clinical Cooperative Group Leukemia, Helmholtz Zentrum München, German Research Center for Environmental Health
    German Cancer Consortium (DKTK)
    German Cancer Research Center (DKFZ))

  • Sayantanee Dutta

    (University Hospital, Ludwig-Maximilians-Universität (LMU) München
    Clinical Cooperative Group Leukemia, Helmholtz Zentrum München, German Research Center for Environmental Health
    German Cancer Consortium (DKTK)
    German Cancer Research Center (DKFZ))

  • Sabrina Opatz

    (University Hospital, Ludwig-Maximilians-Universität (LMU) München
    Clinical Cooperative Group Leukemia, Helmholtz Zentrum München, German Research Center for Environmental Health
    German Cancer Consortium (DKTK)
    German Cancer Research Center (DKFZ))

  • Sebastian Vosberg

    (University Hospital, Ludwig-Maximilians-Universität (LMU) München
    Clinical Cooperative Group Leukemia, Helmholtz Zentrum München, German Research Center for Environmental Health
    German Cancer Consortium (DKTK)
    German Cancer Research Center (DKFZ))

  • Katrin Reiter

    (University Hospital, Ludwig-Maximilians-Universität (LMU) München
    Clinical Cooperative Group Leukemia, Helmholtz Zentrum München, German Research Center for Environmental Health
    German Cancer Consortium (DKTK)
    German Cancer Research Center (DKFZ))

  • Georg Leubolt

    (University Hospital, Ludwig-Maximilians-Universität (LMU) München
    Clinical Cooperative Group Leukemia, Helmholtz Zentrum München, German Research Center for Environmental Health
    German Cancer Consortium (DKTK)
    German Cancer Research Center (DKFZ))

  • Klaus H. Metzeler

    (University Hospital, Ludwig-Maximilians-Universität (LMU) München
    Clinical Cooperative Group Leukemia, Helmholtz Zentrum München, German Research Center for Environmental Health
    German Cancer Consortium (DKTK)
    German Cancer Research Center (DKFZ))

  • Tobias Herold

    (University Hospital, Ludwig-Maximilians-Universität (LMU) München
    Clinical Cooperative Group Leukemia, Helmholtz Zentrum München, German Research Center for Environmental Health
    German Cancer Consortium (DKTK)
    German Cancer Research Center (DKFZ))

  • Stefanos A. Bamopoulos

    (University Hospital, Ludwig-Maximilians-Universität (LMU) München)

  • Kathrin Bräundl

    (University Hospital, Ludwig-Maximilians-Universität (LMU) München
    Clinical Cooperative Group Leukemia, Helmholtz Zentrum München, German Research Center for Environmental Health
    German Cancer Consortium (DKTK)
    German Cancer Research Center (DKFZ))

  • Evelyn Zellmeier

    (University Hospital, Ludwig-Maximilians-Universität (LMU) München)

  • Bianka Ksienzyk

    (University Hospital, Ludwig-Maximilians-Universität (LMU) München)

  • Nikola P. Konstandin

    (University Hospital, Ludwig-Maximilians-Universität (LMU) München)

  • Stephanie Schneider

    (University Hospital, Ludwig-Maximilians-Universität (LMU) München)

  • Karl-Peter Hopfner

    (Ludwig-Maximilians-Universität (LMU) München)

  • Alexander Graf

    (Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, Ludwig-Maximilians-Universität (LMU) München)

  • Stefan Krebs

    (Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, Ludwig-Maximilians-Universität (LMU) München)

  • Helmut Blum

    (German Cancer Consortium (DKTK)
    German Cancer Research Center (DKFZ)
    Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, Ludwig-Maximilians-Universität (LMU) München)

  • Jan Moritz Middeke

    (German Cancer Consortium (DKTK)
    German Cancer Research Center (DKFZ)
    Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden)

  • Friedrich Stölzel

    (German Cancer Consortium (DKTK)
    German Cancer Research Center (DKFZ)
    Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden)

  • Christian Thiede

    (German Cancer Consortium (DKTK)
    German Cancer Research Center (DKFZ)
    Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden)

  • Stephan Wolf

    (German Cancer Research Center (DKFZ))

  • Stefan K. Bohlander

    (The University of Auckland)

  • Caroline Preiss

    (Cell Therapeutics and Hemostasis, University Hospital, Ludwig-Maximilians-Universität (LMU) München)

  • Linping Chen-Wichmann

    (Cell Therapeutics and Hemostasis, University Hospital, Ludwig-Maximilians-Universität (LMU) München)

  • Christian Wichmann

    (Cell Therapeutics and Hemostasis, University Hospital, Ludwig-Maximilians-Universität (LMU) München)

  • Maria Cristina Sauerland

    (Institute of Biostatistics and Clinical Research, University of Münster)

  • Thomas Büchner

    (Hematology, Oncology and Pneumology, University of Münster)

  • Wolfgang E. Berdel

    (Hematology, Oncology and Pneumology, University of Münster)

  • Bernhard J. Wörmann

    (Oncology and Tumor Immunology, Charité University Medicine, Campus Virchow)

  • Jan Braess

    (Oncology and Hematology, St. John-of-God Hospital)

  • Wolfgang Hiddemann

    (University Hospital, Ludwig-Maximilians-Universität (LMU) München
    Clinical Cooperative Group Leukemia, Helmholtz Zentrum München, German Research Center for Environmental Health
    German Cancer Consortium (DKTK)
    German Cancer Research Center (DKFZ))

  • Karsten Spiekermann

    (University Hospital, Ludwig-Maximilians-Universität (LMU) München
    Clinical Cooperative Group Leukemia, Helmholtz Zentrum München, German Research Center for Environmental Health
    German Cancer Consortium (DKTK)
    German Cancer Research Center (DKFZ))

  • Philipp A. Greif

    (University Hospital, Ludwig-Maximilians-Universität (LMU) München
    Clinical Cooperative Group Leukemia, Helmholtz Zentrum München, German Research Center for Environmental Health
    German Cancer Consortium (DKTK)
    German Cancer Research Center (DKFZ))

Abstract

The t(8;21) translocation is one of the most frequent cytogenetic abnormalities in acute myeloid leukaemia (AML) and results in the RUNX1/RUNX1T1 rearrangement. Despite the causative role of the RUNX1/RUNX1T1 fusion gene in leukaemia initiation, additional genetic lesions are required for disease development. Here we identify recurring ZBTB7A mutations in 23% (13/56) of AML t(8;21) patients, including missense and truncating mutations resulting in alteration or loss of the C-terminal zinc-finger domain of ZBTB7A. The transcription factor ZBTB7A is important for haematopoietic lineage fate decisions and for regulation of glycolysis. On a functional level, we show that ZBTB7A mutations disrupt the transcriptional repressor potential and the anti-proliferative effect of ZBTB7A. The specific association of ZBTB7A mutations with t(8;21) rearranged AML points towards leukaemogenic cooperativity between mutant ZBTB7A and the RUNX1/RUNX1T1 fusion.

Suggested Citation

  • Luise Hartmann & Sayantanee Dutta & Sabrina Opatz & Sebastian Vosberg & Katrin Reiter & Georg Leubolt & Klaus H. Metzeler & Tobias Herold & Stefanos A. Bamopoulos & Kathrin Bräundl & Evelyn Zellmeier , 2016. "ZBTB7A mutations in acute myeloid leukaemia with t(8;21) translocation," Nature Communications, Nature, vol. 7(1), pages 1-7, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11733
    DOI: 10.1038/ncomms11733
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