JDP2: An oncogenic bZIP transcription factor in T cell acute lymphoblastic leukemia.
JDP2: An oncogenic bZIP transcription factor in T cell acute lymphoblastic leukemia.
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DOI：
10.1084/jem.20170484
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发表时间：
2018-07-02
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影响因子：
--
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作者：
Mansour MR;He S;Li Z;Lobbardi R;Abraham BJ;Hug C;Rahman S;Leon TE;Kuang YY;Zimmerman MW;Blonquist T;Gjini E;Gutierrez A;Tang Q;Garcia-Perez L;Pike-Overzet K;Anders L;Berezovskaya A;Zhou Y;Zon LI;Neuberg D;Fielding AK;Staal FJT;Langenau DM;Sanda T;Young RA;Look AT
Mansour等人证实bZIP转录因子JDP2在高危T细胞急性淋巴细胞白血病（T- all）患者中过表达。JDP2在斑马鱼模型中启动T-ALL，并通过直接调控MCL1导致体内类固醇耐药。相当一部分T细胞急性淋巴细胞白血病（T- all）患者对类固醇产生耐药性并死于疾病。JDP2编码一种bZIP蛋白，该蛋白与小鼠插入突变研究中发现的T-ALL癌基因有关，但其在人类T-ALL发病机制中的作用仍不清楚。在这里，我们发现JDP2在T-ALL患者的一个亚群中异常表达，并与较差的生存率相关。JDP2是T-ALL细胞存活所必需的，因为短发夹RNA敲除会导致其凋亡。在机制上，JDP2通过直接转录调控MCL1调控促生存信号。此外，JDP2是少数几个能够在转基因斑马鱼中启动T-ALL的癌基因之一。值得注意的是，rag2:jdp2转基因斑马鱼的胸腺细胞在体内表达高水平的mcl1，并表现出对类固醇的抗性。这些研究证实了JDP2在高危T-ALL中是一个新的致癌基因，并暗示MCL1的过表达是JDP2过表达细胞中类固醇耐药的机制。
Mansour et al. demonstrate that JDP2, a bZIP transcription factor, is overexpressed in patients with high-risk T cell acute lymphoblastic leukemia (T-ALL). JDP2 initiates T-ALL in a zebrafish model and leads to steroid resistance in vivo through direct regulation of MCL1. A substantial subset of patients with T cell acute lymphoblastic leukemia (T-ALL) develops resistance to steroids and succumbs to their disease. JDP2 encodes a bZIP protein that has been implicated as a T-ALL oncogene from insertional mutagenesis studies in mice, but its role in human T-ALL pathogenesis has remained obscure. Here we show that JDP2 is aberrantly expressed in a subset of T-ALL patients and is associated with poor survival. JDP2 is required for T-ALL cell survival, as its depletion by short hairpin RNA knockdown leads to apoptosis. Mechanistically, JDP2 regulates prosurvival signaling through direct transcriptional regulation of MCL1. Furthermore, JDP2 is one of few oncogenes capable of initiating T-ALL in transgenic zebrafish. Notably, thymocytes from rag2:jdp2 transgenic zebrafish express high levels of mcl1 and demonstrate resistance to steroids in vivo. These studies establish JDP2 as a novel oncogene in high-risk T-ALL and implicate overexpression of MCL1 as a mechanism of steroid resistance in JDP2-overexpressing cells.
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影响因子：
50.3
作者：
Blackburn JS;Liu S;Wilder JL;Dobrinski KP;Lobbardi R;Moore FE;Martinez SA;Chen EY;Lee C;Langenau DM
通讯作者：
Langenau DM
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
11.4
作者：
Delgado-Martin C;Meyer LK;Huang BJ;Shimano KA;Zinter MS;Nguyen JV;Smith GA;Taunton J;Winter SS;Roderick JR;Kelliher MA;Horton TM;Wood BL;Teachey DT;Hermiston ML
通讯作者：
Hermiston ML
影响因子：
10.1
作者：
Aries, Ingrid M.;Hansen, Bo R.;den Boer, Monique L.
通讯作者：
den Boer, Monique L.
DOI：
10.1084/jem.20042524
发表时间：
2005-06-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dik WA;Pike-Overzet K;Weerkamp F;de Ridder D;de Haas EF;Baert MR;van der Spek P;Koster EE;Reinders MJ;van Dongen JJ;Langerak AW;Staal FJ
通讯作者：
Staal FJ