Deregulation of DUX4 and ERG in acute lymphoblastic leukemia.
Deregulation of DUX4 and ERG in acute lymphoblastic leukemia.
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DOI：
10.1038/ng.3691
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发表时间：
2016-12
期刊：
影响因子：
30.8
通讯作者：
Mullighan, Charles G.
中科院分区：
文献类型：
--
作者：
Zhang, Jinghui;McCastlain, Kelly;Yoshihara, Hiroki;Xu, Beisi;Chang, Yunchao;Churchman, Michelle L.;Wul, Gang;Li, Yongjin;Wei, Lei;Iacobucci, Ilaria;Liu, Yu;Qu, Chunxu;Wen, Ji;Edmonsonl, Michael;Payne-Turner, Debbie;Kaufmann, Kerstin B.;Takayanagi, Shin-ichiro;Wienholds, Erno;Waanders, Esme;Ntziachristos, Panagiotis;Bakogianni, Sofia;Wang, Jingjing;Aifantis, Iannis;Roberts, Kathryn G.;Ma, Jing;Song, Guangchun;Easton, John;Mulder, Heather L.;Chen, Xiang;Newman, Scott;Ma, Xiaotu;Rusch, Michael;Gupta, Pankaj;Boggs, Kristy;Vadodaria, Bhavin;Dalton, James;Liu, Yanling;Valentine, Marcus L.;Ding, Li;Lu, Charles;Fulton, Robert S.;Fulton, Lucinda;Tabib, Yashodhan;Ochoa, Kerri;Devidas, Meenakshi;Pei, Deqing;Cheng, Cheng;Yang, Jun;Evans, William E.;Relling, Mary V.;Pui, Ching-Hon;Jeha, Sima;Harvey, Richard C.;Chen, I-Ming L.;Willman, Cheryl L.;Marcucci, Guido;Bloomfield, Clara D.;Kohlschmidt, Jessica;Mrozek, Krzysztof;Paietta, Elisabeth;Tallman, Martin S.;Stock, Wendy;Foster, Matthew C.;Racevskis, Janis;Rowe, Jacob M.;Luger, Selina;Kornblau, Steven M.;Shurtleff, Sheila A.;Raimondi, Susana C.;Mardis, Elaine R.;Wilson, Richard K.;Dick, John E.;Hunger, Stephen P.;Loh, Mignon L.;Downing, James R.;Mullighan, Charles G.
染色体重排失调造血转录因子是常见的急性淋巴细胞白血病（ALL）。在这里，我们表明，同源异型盒转录因子基因DUX 4和ETS转录因子基因ERG的失调是一个亚型的B祖细胞ALL，包括高达7%的B-ALL的标志。DUX 4重排和过表达存在于所有病例中，并伴随着ERG的转录失调，一种新的ERG亚型ERGalt的表达和频繁的ERG缺失。ERGalt利用非典型的第一外显子，其转录由DUX 4结合启动。ERGalt保留ERG的DNA结合和反式激活结构域，但抑制野生型ERG转录活性并进行转化。这些结果说明了白血病中转录因子失调的独特范例，其中DUX 4失调通过缺失或诱导作为野生型ERG功能的显性负抑制剂的同种型的表达而导致ERG功能丧失。
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 are hallmarks 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 utilizes a non-canonical first exon whose transcription was initiated by DUX4 binding. ERGalt retains the DNA-binding and transactivating domains of ERG, but 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 induction of expression of an isoform that is a dominant negative inhibitor of wild type ERG function.
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影响因子：
3.7
作者：
Kneissl S;Abel T;Rasbach A;Brynza J;Schneider-Schaulies J;Buchholz CJ
通讯作者：
Buchholz CJ
影响因子：
64.8
作者：
Mullighan, Charles G.;Goorha, Salil;Downing, James R.
通讯作者：
Downing, James R.
影响因子：
20.3
作者：
Harvey, Richard C.;Mullighan, Charles G.;Willman, Cheryl L.
通讯作者：
Willman, Cheryl L.
影响因子：
30.5
作者：
Loughran, Stephen J.;Kruse, Elizabeth A.;Kile, Benjamin T.
通讯作者：
Kile, Benjamin T.
影响因子：
3.6
作者：
Mullighan CG
通讯作者：
Mullighan CG