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Hartmann, L. ; Dutta, S. ; Opatz, S. ; Vosberg, S. ; Reiter, K. ; Leubolt, G. ; Metzeler, K.H. ; Herold, T. ; Bamopoulos, S.A.* ; Bräundl, K.* ; Zellmeier, E.* ; Ksienzyk, B.* ; Konstandin, N.P.* ; Schneider, S.* ; Hopfner, K.P.* ; Graf, A.* ; Krebs, S.* ; Blum, H.* ; Middeke, J.M.* ; Stölzel, F.* ; Thiede, C.* ; Wolf, S.* ; Bohlander, S.K.* ; Preiss, C.* ; Chen-Wichmann, L.* ; Wichmann, C.* ; Sauerland, M.C.* ; Büchner, T.* ; Berdel, W.E.* ; Wörmann, B.J.* ; Braess, J.* ; Hiddemann, W. ; Spiekermann, K. ; Greif, P.A.

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

Nat. Commun. 7:11733 (2016)
Publ. Version/Full Text Supplement DOI
Open Access Gold
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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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Tumor-suppressor; Aml1-eto; Gene; Expression; Repression; Protein; Domain; Fbi-1; Identification; Transformation
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Quellenangaben Volume: 7, Issue: , Pages: , Article Number: 11733 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed