Global Identification of EVI1 Target Genes in Acute Myeloid Leukemia.
Global Identification of EVI1 Target Genes in Acute Myeloid Leukemia.
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DOI：
10.1371/journal.pone.0067134
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Perkins A
中科院分区：
文献类型：
--
作者：
Glass C;Wuertzer C;Cui X;Bi Y;Davuluri R;Xiao YY;Wilson M;Owens K;Zhang Y;Perkins A
亲嗜性病毒整合位点1（EVI1）转录因子与预后不良的人类髓系恶性肿瘤相关，在8 - 10%的成人急性髓系白血病（AML）中过度表达，在儿童混合谱系白血病（MLL）重排白血病中更是高达27%。我们首次结合染色质免疫沉淀测序（ChIP - Seq）和RNA测序（RNA - Seq）表达谱分析，报道了白血病细胞中全面的全基因组EVI1结合情况以及整个转录组基因的失调。我们发现终末髓系分化和细胞周期调控的紊乱在EVI1诱导的白血病发生过程中十分显著。具体而言，我们确定EVI1直接结合并下调主髓系分化基因Cebpe及其对终末髓系分化至关重要的几个下游基因靶点。我们还发现EVI1结合并下调Serpinb2以及众多参与Jak - Stat信号通路的基因。最后，我们确定了几个参与凋亡机制的ATP依赖型P2X嘌呤受体基因表达降低。这些发现为未来研究EVI1诱导的白血病的潜在治疗性基因靶点奠定了基础。
The ecotropic virus integration site 1 (EVI1) transcription factor is associated with human myeloid malignancy of poor prognosis and is overexpressed in 8–10% of adult AML and strikingly up to 27% of pediatric MLL-rearranged leukemias. For the first time, we report comprehensive genomewide EVI1 binding and whole transcriptome gene deregulation in leukemic cells using a combination of ChIP-Seq and RNA-Seq expression profiling. We found disruption of terminal myeloid differentiation and cell cycle regulation to be prominent in EVI-induced leukemogenesis. Specifically, we identified EVI1 directly binds to and downregulates the master myeloid differentiation gene Cebpe and several of its downstream gene targets critical for terminal myeloid differentiation. We also found EVI1 binds to and downregulates Serpinb2 as well as numerous genes involved in the Jak-Stat signaling pathway. Finally, we identified decreased expression of several ATP-dependent P2X purinoreceptors genes involved in apoptosis mechanisms. These findings provide a foundation for future study of potential therapeutic gene targets for EVI1-induced leukemia.
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影响因子：
3.7
作者：
Akagi T;Thoennissen NH;George A;Crooks G;Song JH;Okamoto R;Nowak D;Gombart AF;Koeffler HP
通讯作者：
Koeffler HP
DOI：
10.1073/pnas.1119229109
发表时间：
2012-02-07
影响因子：
11.1
作者：
Bard-Chapeau, Emilie A.;Jeyakani, Justin;Copeland, Neal G.
通讯作者：
Copeland, Neal G.
影响因子：
4.8
作者：
Chakraborty, S;Senyuk, V;Nucifora, G
通讯作者：
Nucifora, G
影响因子：
11.4
作者：
Balgobind, B. V.;Lugthart, S.;van den Heuvel-Eibrink, M. M.
通讯作者：
van den Heuvel-Eibrink, M. M.
影响因子：
20.3
作者：
Gombart, AF;Kwok, SH;Koeffler, HP
通讯作者：
Koeffler, HP