Title |
Deregulation of DUX4 and ERG in acute lymphoblastic leukemia
|
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Published in |
Nature Genetics, October 2016
|
DOI | 10.1038/ng.3691 |
Pubmed ID | |
Authors |
Jinghui Zhang, Kelly McCastlain, Hiroki Yoshihara, Beisi Xu, Yunchao Chang, Michelle L Churchman, Gang Wu, Yongjin Li, Lei Wei, Ilaria Iacobucci, Yu Liu, Chunxu Qu, Ji Wen, Michael Edmonson, Debbie Payne-Turner, Kerstin B Kaufmann, Shin-ichiro Takayanagi, Erno Wienholds, Esmé Waanders, Panagiotis Ntziachristos, Sofia Bakogianni, Jingjing Wang, Iannis Aifantis, Kathryn G Roberts, Jing Ma, Guangchun Song, John Easton, Heather L Mulder, Xiang Chen, Scott Newman, Xiaotu Ma, Michael Rusch, Pankaj Gupta, Kristy Boggs, Bhavin Vadodaria, James Dalton, Yanling Liu, Marcus L Valentine, Li Ding, Charles Lu, Robert S Fulton, Lucinda Fulton, Yashodhan Tabib, Kerri Ochoa, Meenakshi Devidas, Deqing Pei, Cheng Cheng, Jun Yang, William E Evans, Mary V Relling, Ching-Hon Pui, Sima Jeha, Richard C Harvey, I-Ming L Chen, Cheryl L Willman, Guido Marcucci, Clara D Bloomfield, Jessica Kohlschmidt, Krzysztof Mrózek, Elisabeth Paietta, Martin S Tallman, Wendy Stock, Matthew C Foster, Janis Racevskis, Jacob M Rowe, Selina Luger, Steven M Kornblau, Sheila A Shurtleff, Susana C Raimondi, Elaine R Mardis, Richard K Wilson, John E Dick, Stephen P Hunger, Mignon L Loh, James R Downing, Charles G Mullighan |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 13 | 48% |
Japan | 1 | 4% |
United Kingdom | 1 | 4% |
China | 1 | 4% |
Austria | 1 | 4% |
Finland | 1 | 4% |
El Salvador | 1 | 4% |
Unknown | 8 | 30% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Scientists | 17 | 63% |
Members of the public | 8 | 30% |
Science communicators (journalists, bloggers, editors) | 2 | 7% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 1 | <1% |
United States | 1 | <1% |
Unknown | 259 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 50 | 19% |
Student > Ph. D. Student | 48 | 18% |
Student > Master | 37 | 14% |
Student > Bachelor | 19 | 7% |
Other | 17 | 7% |
Other | 39 | 15% |
Unknown | 51 | 20% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 80 | 31% |
Medicine and Dentistry | 54 | 21% |
Agricultural and Biological Sciences | 39 | 15% |
Immunology and Microbiology | 5 | 2% |
Computer Science | 4 | 2% |
Other | 17 | 7% |
Unknown | 62 | 24% |