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

Luise Hartmann, Sayantanee Dutta, Sabrina Opatz, Sebastian Vosberg, Katrin Reiter, Georg Leubolt, Klaus H. Metzeler, Tobias Herold, Stefanos A. Bamopoulos, Kathrin Bräundl, Evelyn Zellmeier, Bianka Ksienzyk, Nikola P. Konstandin, Stephanie Schneider, Karl-Peter Hopfner, Alexander Graf, Stefan Krebs, Helmut Blum, Jan Moritz Middeke, Friedrich Stölzel, Christian Thiede, Stephan Wolf, Stefan K. Bohlander, Caroline Preiss, Linping Chen-Wichmann, Christian Wichmann, Maria Cristina Sauerland, Thomas Büchner, Wolfgang E. Berdel, Bernhard J. Wörmann, Jan Braess, Wolfgang Hiddemann, Karsten Spiekermann and Philipp A. Greif ()
Additional contact information
Luise Hartmann: University Hospital, Ludwig-Maximilians-Universität (LMU) München
Sayantanee Dutta: University Hospital, Ludwig-Maximilians-Universität (LMU) München
Sabrina Opatz: University Hospital, Ludwig-Maximilians-Universität (LMU) München
Sebastian Vosberg: University Hospital, Ludwig-Maximilians-Universität (LMU) München
Katrin Reiter: University Hospital, Ludwig-Maximilians-Universität (LMU) München
Georg Leubolt: University Hospital, Ludwig-Maximilians-Universität (LMU) München
Klaus H. Metzeler: University Hospital, Ludwig-Maximilians-Universität (LMU) München
Tobias Herold: University Hospital, Ludwig-Maximilians-Universität (LMU) München
Stefanos A. Bamopoulos: University Hospital, Ludwig-Maximilians-Universität (LMU) München
Kathrin Bräundl: University Hospital, Ludwig-Maximilians-Universität (LMU) München
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)
Jan Moritz Middeke: German Cancer Consortium (DKTK)
Friedrich Stölzel: German Cancer Consortium (DKTK)
Christian Thiede: German Cancer Consortium (DKTK)
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
Karsten Spiekermann: University Hospital, Ludwig-Maximilians-Universität (LMU) München
Philipp A. Greif: University Hospital, Ludwig-Maximilians-Universität (LMU) München

Nature Communications, 2016, vol. 7, issue 1, 1-7

Abstract: 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.

Date: 2016
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11733

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DOI: 10.1038/ncomms11733

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