| Literature DB >> 27776115 |
Jinghui Zhang1, Kelly McCastlain2, Hiroki Yoshihara2, Beisi Xu1, Yunchao Chang2, Michelle L Churchman2, Gang Wu1, Yongjin Li1, Lei Wei1,2, Ilaria Iacobucci2, Yu Liu1, Chunxu Qu1, Ji Wen1, Michael Edmonson1, Debbie Payne-Turner2, Kerstin B Kaufmann3, Shin-Ichiro Takayanagi3,4, Erno Wienholds3, Esmé Waanders2,5, Panagiotis Ntziachristos6, Sofia Bakogianni6, Jingjing Wang6, Iannis Aifantis6,7, Kathryn G Roberts2, Jing Ma2, Guangchun Song2, John Easton1, Heather L Mulder1, Xiang Chen1, Scott Newman1, Xiaotu Ma1, Michael Rusch1, Pankaj Gupta1, Kristy Boggs1, Bhavin Vadodaria1, James Dalton2, Yanling Liu2, Marcus L Valentine8, Li Ding9, Charles Lu9, Robert S Fulton9, Lucinda Fulton9, Yashodhan Tabib9, Kerri Ochoa9, Meenakshi Devidas10, Deqing Pei11, Cheng Cheng11, Jun Yang12, William E Evans12, Mary V Relling12, Ching-Hon Pui13, Sima Jeha13, Richard C Harvey14, I-Ming L Chen14, Cheryl L Willman14, Guido Marcucci15, Clara D Bloomfield16, Jessica Kohlschmidt16, Krzysztof Mrózek16, Elisabeth Paietta17, Martin S Tallman18, Wendy Stock19, Matthew C Foster20, Janis Racevskis21, Jacob M Rowe22, Selina Luger23, Steven M Kornblau24, Sheila A Shurtleff2, Susana C Raimondi2, Elaine R Mardis9, Richard K Wilson9, John E Dick3, Stephen P Hunger25, Mignon L Loh26, James R Downing2, Charles G Mullighan2.
Abstract
Chromosomal rearrangements deregulating hematopoietic transcription factors are common in acute lymphoblastic leukemia (ALL). Here we show that deregulation of the homeobox transcription factor gene DUX4 and the ETS transcription factor gene ERG is a hallmark of a subtype of B-progenitor ALL that comprises up to 7% of B-ALL. DUX4 rearrangement and overexpression was present in all cases and was accompanied by transcriptional deregulation of ERG, expression of a novel ERG isoform, ERGalt, and frequent ERG deletion. ERGalt uses a non-canonical first exon whose transcription was initiated by DUX4 binding. ERGalt retains the DNA-binding and transactivation domains of ERG, but it inhibits wild-type ERG transcriptional activity and is transforming. These results illustrate a unique paradigm of transcription factor deregulation in leukemia in which DUX4 deregulation results in loss of function of ERG, either by deletion or induced expression of an isoform that is a dominant-negative inhibitor of wild-type ERG function.Entities:
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Year: 2016 PMID： 27776115 PMCID： PMC5144107 DOI： 10.1038/ng.3691
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330