{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T06:33:40Z","timestamp":1791614020887,"version":"4.3.4"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,6,2]],"date-time":"2016-06-02T00:00:00Z","timestamp":1464825600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,6,2]],"date-time":"2016-06-02T00:00:00Z","timestamp":1464825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The t(8;21) translocation is one of the most frequent cytogenetic abnormalities in acute myeloid leukaemia (AML) and results in the <jats:italic>RUNX1<\/jats:italic>\/<jats:italic>RUNX1T1<\/jats:italic> rearrangement. Despite the causative role of the <jats:italic>RUNX1<\/jats:italic>\/<jats:italic>RUNX1T1<\/jats:italic> fusion gene in leukaemia initiation, additional genetic lesions are required for disease development. Here we identify recurring <jats:italic>ZBTB7A<\/jats:italic> 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 <jats:italic>ZBTB7A<\/jats:italic> mutations disrupt the transcriptional repressor potential and the anti-proliferative effect of ZBTB7A. The specific association of <jats:italic>ZBTB7A<\/jats:italic> mutations with t(8;21) rearranged AML points towards leukaemogenic cooperativity between mutant ZBTB7A and the RUNX1\/RUNX1T1 fusion.<\/jats:p>","DOI":"10.1038\/ncomms11733","type":"journal-article","created":{"date-parts":[[2016,6,2]],"date-time":"2016-06-02T10:56:51Z","timestamp":1464865011000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["ZBTB7A mutations in acute myeloid leukaemia with t(8;21) translocation"],"prefix":"10.1038","volume":"7","author":[{"given":"Luise","family":"Hartmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayantanee","family":"Dutta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Opatz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Vosberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Reiter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Leubolt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus H.","family":"Metzeler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Herold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanos A.","family":"Bamopoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Br\u00e4undl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyn","family":"Zellmeier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianka","family":"Ksienzyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikola P.","family":"Konstandin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl-Peter","family":"Hopfner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Graf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Krebs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Blum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Moritz","family":"Middeke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedrich","family":"St\u00f6lzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Thiede","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan K.","family":"Bohlander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Preiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linping","family":"Chen-Wichmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Wichmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina","family":"Sauerland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"B\u00fcchner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang E.","family":"Berdel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard J.","family":"W\u00f6rmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Braess","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Hiddemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karsten","family":"Spiekermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp A.","family":"Greif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,6,2]]},"reference":[{"key":"BFncomms11733_CR1","first-page":"109","volume":"16","author":"JD Rowley","year":"1973","unstructured":"Rowley, J. D. Identificaton of a translocation with quinacrine fluorescence in a patient with acute leukemia. Ann. Genet. 16, 109\u2013112 (1973).","journal-title":"Ann. Genet."},{"key":"BFncomms11733_CR2","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1182\/blood.V80.7.1825.1825","volume":"80","author":"P Erickson","year":"1992","unstructured":"Erickson, P. et al. Identification of breakpoints in t(8;21) acute myelogenous leukemia and isolation of a fusion transcript, AML1\/ETO, with similarity to Drosophila segmentation gene, runt. Blood 80, 1825\u20131831 (1992).","journal-title":"Blood"},{"key":"BFncomms11733_CR3","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1182\/blood-2009-03-209262","volume":"114","author":"JW Vardiman","year":"2009","unstructured":"Vardiman, J. W. et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 114, 937\u2013951 (2009).","journal-title":"Blood"},{"key":"BFncomms11733_CR4","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1182\/blood.V96.6.2108","volume":"96","author":"KL Rhoades","year":"2000","unstructured":"Rhoades, K. L. et al. Analysis of the role of AML1-ETO in leukemogenesis, using an inducible transgenic mouse model. Blood 96, 2108\u20132115 (2000).","journal-title":"Blood"},{"key":"BFncomms11733_CR5","doi-asserted-by":"publisher","first-page":"2159","DOI":"10.1172\/JCI24225","volume":"115","author":"C Schessl","year":"2005","unstructured":"Schessl, C. et al. The AML1-ETO fusion gene and the FLT3 length mutation collaborate in inducing acute leukemia in mice. J. Clin. Invest. 115, 2159\u20132168 (2005).","journal-title":"J. Clin. Invest."},{"key":"BFncomms11733_CR6","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1084\/jem.20020824","volume":"196","author":"M Schwieger","year":"2002","unstructured":"Schwieger, M. et al. AML1-ETO inhibits maturation of multiple lymphohematopoietic lineages and induces myeloblast transformation in synergy with ICSBP deficiency. J. Exp. Med. 196, 1227\u20131240 (2002).","journal-title":"J. Exp. Med."},{"key":"BFncomms11733_CR7","doi-asserted-by":"publisher","first-page":"10398","DOI":"10.1073\/pnas.171321298","volume":"98","author":"Y Yuan","year":"2001","unstructured":"Yuan, Y. et al. AML1-ETO expression is directly involved in the development of acute myeloid leukemia in the presence of additional mutations. Proc. Natl Acad. Sci. USA 98, 10398\u201310403 (2001).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms11733_CR8","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/S1535-6108(02)00016-8","volume":"1","author":"M Higuchi","year":"2002","unstructured":"Higuchi, M. et al. Expression of a conditional AML1-ETO oncogene bypasses embryonic lethality and establishes a murine model of human t(8;21) acute myeloid leukemia. Cancer Cell 1, 63\u201374 (2002).","journal-title":"Cancer Cell"},{"key":"BFncomms11733_CR9","doi-asserted-by":"publisher","first-page":"2845","DOI":"10.1182\/blood-2012-11-292037","volume":"121","author":"A Lunardi","year":"2013","unstructured":"Lunardi, A., Guarnerio, J., Wang, G., Maeda, T. & Pandolfi, P. P. Role of LRF\/Pokemon in lineage fate decisions. Blood 121, 2845\u20132853 (2013).","journal-title":"Blood"},{"key":"BFncomms11733_CR10","doi-asserted-by":"publisher","first-page":"1917","DOI":"10.1101\/gad.245910.114","volume":"28","author":"XS Liu","year":"2014","unstructured":"Liu, X. S. et al. ZBTB7A acts as a tumor suppressor through the transcriptional repression of glycolysis. Genes Dev. 28, 1917\u20131928 (2014).","journal-title":"Genes Dev."},{"key":"BFncomms11733_CR11","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1093\/bfgp\/elm002","volume":"6","author":"JA Costoya","year":"2007","unstructured":"Costoya, J. A. Functional analysis of the role of POK transcriptional repressors. Brief Funct. Genomic Proteomic 6, 8\u201318 (2007).","journal-title":"Brief Funct. Genomic Proteomic"},{"key":"BFncomms11733_CR12","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1093\/nar\/27.5.1251","volume":"27","author":"DJ Morrison","year":"1999","unstructured":"Morrison, D. J. et al. FBI-1, a factor that binds to the HIV-1 inducer of short transcripts (IST), is a POZ domain protein. Nucleic Acids Res. 27, 1251\u20131262 (1999).","journal-title":"Nucleic Acids Res."},{"key":"BFncomms11733_CR13","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.1182\/blood-2014-04-571018","volume":"124","author":"JB Micol","year":"2014","unstructured":"Micol, J. B. et al. Frequent ASXL2 mutations in acute myeloid leukemia patients with t(8;21)\/RUNX1-RUNX1T1 chromosomal translocations. Blood 124, 1445\u20131449 (2014).","journal-title":"Blood"},{"key":"BFncomms11733_CR14","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1038\/nature03203","volume":"433","author":"T Maeda","year":"2005","unstructured":"Maeda, T. et al. Role of the proto-oncogene Pokemon in cellular transformation and ARF repression. Nature 433, 278\u2013285 (2005).","journal-title":"Nature"},{"key":"BFncomms11733_CR15","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1091\/mbc.01-08-0383","volume":"13","author":"PS Pendergrast","year":"2002","unstructured":"Pendergrast, P. S., Wang, C., Hernandez, N. & Huang, S. FBI-1 can stimulate HIV-1 Tat activity and is targeted to a novel subnuclear domain that includes the Tat-P-TEFb-containing nuclear speckles. Mol. Biol. Cell 13, 915\u2013929 (2002).","journal-title":"Mol. Biol. Cell"},{"key":"BFncomms11733_CR16","doi-asserted-by":"publisher","first-page":"1617","DOI":"10.1056\/NEJMoa040465","volume":"350","author":"PJ Valk","year":"2004","unstructured":"Valk, P. J. et al. Prognostically useful gene-expression profiles in acute myeloid leukemia. N. Engl. J. Med. 350, 1617\u20131628 (2004).","journal-title":"N. Engl. J. Med."},{"key":"BFncomms11733_CR17","doi-asserted-by":"publisher","first-page":"3088","DOI":"10.1182\/blood-2008-09-179895","volume":"113","author":"BJ Wouters","year":"2009","unstructured":"Wouters, B. J. et al. Double CEBPA mutations, but not single CEBPA mutations, define a subgroup of acute myeloid leukemia with a distinctive gene expression profile that is uniquely associated with a favorable outcome. Blood 113, 3088\u20133091 (2009).","journal-title":"Blood"},{"key":"BFncomms11733_CR18","doi-asserted-by":"crossref","unstructured":"Lavall\u00e9e, V.-P. et al. RNA-sequencing analysis of core binding factor AML identifies recurrent ZBTB7A mutations and defines RUNX1-CBFA2T3 fusion signature. Blood, pii: blood-2016-03-703868 (2016).","DOI":"10.1182\/blood-2016-03-703868"},{"key":"BFncomms11733_CR19","doi-asserted-by":"publisher","first-page":"33199","DOI":"10.1074\/jbc.M802935200","volume":"283","author":"BN Jeon","year":"2008","unstructured":"Jeon, B. N. et al. Proto-oncogene FBI-1 (Pokemon\/ZBTB7A) represses transcription of the tumor suppressor Rb gene via binding competition with Sp1 and recruitment of co-repressors. J. Biol. Chem. 283, 33199\u201333210 (2008).","journal-title":"J. Biol. Chem."},{"key":"BFncomms11733_CR20","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1038\/ng.2654","volume":"45","author":"G Wang","year":"2013","unstructured":"Wang, G. et al. Zbtb7a suppresses prostate cancer through repression of a Sox9-dependent pathway for cellular senescence bypass and tumor invasion. Nat. Genet. 45, 739\u2013746 (2013).","journal-title":"Nat. Genet."},{"key":"BFncomms11733_CR21","doi-asserted-by":"crossref","unstructured":"Liu, X. S. et al. Somatic human ZBTB7A zinc finger mutations promote cancer progression. Oncogene, doi:10.1038\/onc.2015.371 (2015).","DOI":"10.1038\/onc.2015.371"},{"key":"BFncomms11733_CR22","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1126\/science.1140881","volume":"316","author":"T Maeda","year":"2007","unstructured":"Maeda, T. et al. Regulation of B versus T lymphoid lineage fate decision by the proto-oncogene LRF. Science 316, 860\u2013866 (2007).","journal-title":"Science"},{"key":"BFncomms11733_CR23","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1016\/j.devcel.2009.09.005","volume":"17","author":"T Maeda","year":"2009","unstructured":"Maeda, T. et al. LRF is an essential downstream target of GATA1 in erythroid development and regulates BIM-dependent apoptosis. Dev. Cell 17, 527\u2013540 (2009).","journal-title":"Dev. Cell"},{"key":"BFncomms11733_CR24","doi-asserted-by":"publisher","first-page":"1304","DOI":"10.1182\/blood-2013-12-540716","volume":"124","author":"T Herold","year":"2014","unstructured":"Herold, T. et al. Isolated trisomy 13 defines a homogeneous AML subgroup with high frequency of mutations in spliceosome genes and poor prognosis. Blood 124, 1304\u20131311 (2014).","journal-title":"Blood"},{"key":"BFncomms11733_CR25","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","volume":"29","author":"A Dobin","year":"2013","unstructured":"Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15\u201321 (2013).","journal-title":"Bioinformatics"},{"key":"BFncomms11733_CR26","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","volume":"31","author":"S Anders","year":"2015","unstructured":"Anders, S., Pyl, P. T. & Huber, W. HTSeq--a Python framework to work with high-throughput sequencing data. Bioinformatics 31, 166\u2013169 (2015).","journal-title":"Bioinformatics"},{"key":"BFncomms11733_CR27","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1002\/prot.22499","volume":"77","author":"A Hildebrand","year":"2009","unstructured":"Hildebrand, A., Remmert, M., Biegert, A. & Soding, J. Fast and accurate automatic structure prediction with HHpred. Proteins 77, (Suppl 9): 128\u2013132 (2009).","journal-title":"Proteins"},{"key":"BFncomms11733_CR28","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1016\/j.jmb.2007.07.017","volume":"372","author":"R Stoll","year":"2007","unstructured":"Stoll, R. et al. Structure of the Wilms tumor suppressor protein zinc finger domain bound to DNA. J. Mol. Biol. 372, 1227\u20131245 (2007).","journal-title":"J. Mol. Biol."},{"key":"BFncomms11733_CR29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-1-4939-0366-5_1","volume":"1137","author":"B Webb","year":"2014","unstructured":"Webb, B. & Sali, A. Protein structure modeling with MODELLER. Methods Mol. Biol. 1137, 1\u201315 (2014).","journal-title":"Methods Mol. Biol."},{"key":"BFncomms11733_CR30","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1038\/leu.2014.179","volume":"29","author":"C Wichmann","year":"2015","unstructured":"Wichmann, C. et al. Activating c-KIT mutations confer oncogenic cooperativity and rescue RUNX1\/ETO-induced DNA damage and apoptosis in human primary CD34+ hematopoietic progenitors. Leukaemia 29, 279\u2013289 (2015).","journal-title":"Leukaemia"},{"key":"BFncomms11733_CR31","doi-asserted-by":"publisher","first-page":"3359","DOI":"10.1093\/bioinformatics\/btv362","volume":"31","author":"W Liu","year":"2015","unstructured":"Liu, W. et al. IBS: an illustrator for the presentation and visualization of biological sequences. Bioinformatics 31, 3359\u20133361 (2015).","journal-title":"Bioinformatics"}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/ncomms11733.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms11733","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms11733.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T11:28:44Z","timestamp":1672831724000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/ncomms11733"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6,2]]},"references-count":31,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,9,1]]}},"alternative-id":["BFncomms11733"],"URL":"https:\/\/doi.org\/10.1038\/ncomms11733","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6,2]]},"assertion":[{"value":"20 October 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 April 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 June 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"11733"}}