The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate.
The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate.
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DOI：
10.1016/j.ccr.2010.01.020
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发表时间：
2010-03-16
期刊：
影响因子：
50.3
通讯作者：
Thompson CB
中科院分区：
文献类型：
--
作者：
Ward PS;Patel J;Wise DR;Abdel-Wahab O;Bennett BD;Coller HA;Cross JR;Fantin VR;Hedvat CV;Perl AE;Rabinowitz JD;Carroll M;Su SM;Sharp KA;Levine RL;Thompson CB
在神经胶质瘤中观察到的胞质异位酸脱氢酶1（IDH1）中的体细胞突变可导致2-羟基氯酸酯（2HG）的产生。在这里，我们报告说，肿瘤2HG的细胞遗传正常急性髓样白血病（AML）的比例高。令人惊讶的是，不到一半的2HG病例具有IDH1突变。其余的2Hg升高病例在IDH2（IDH1的线粒体同源物）中有突变。这些数据表明，所有与癌症相关的IDH突变的共同特征是产生Onco-企业2Hg。此外，具有IDH突变的AML患者显示出其他具有AML相关的突变和/或相关染色体异常的其他特征性良好的染色体，这可能在AML发病机理的独特机制中暗示IDH突变。
The somatic mutations in cytosolic isocitrate dehydrogenase 1 (IDH1) observed in gliomas can lead to the production of 2-hydroxyglutarate (2HG). Here, we report that tumor 2HG is elevated in a high percentage of patients with cytogenetically normal acute myeloid leukemia (AML). Surprisingly, less than half of cases with elevated 2HG possessed IDH1 mutations. The remaining cases with elevated 2HG had mutations in IDH2, the mitochondrial homolog of IDH1. These data demonstrate that a shared feature of all cancer-associated IDH mutations is production of the onco-metabolite 2HG. Furthermore, AML patients with IDH mutations display a significantly reduced number of other well characterized AML-associated mutations and/or associated chromosomal abnormalities, potentially implicating IDH mutation in a distinct mechanism of AML pathogenesis.
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DOI：
10.1126/science.1170944
发表时间：
2009-04-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Zhao S;Lin Y;Xu W;Jiang W;Zha Z;Wang P;Yu W;Li Z;Gong L;Peng Y;Ding J;Lei Q;Guan KL;Xiong Y
通讯作者：
Xiong Y
影响因子：
12.7
作者：
Hartmann, Christian;Meyer, Jochen;von Deimling, Andreas
通讯作者：
von Deimling, Andreas
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
14.8
作者：
Bennett, Bryson D.;Yuan, Jie;Rabinowitz, Joshua D.
通讯作者：
Rabinowitz, Joshua D.
影响因子：
3.4
作者：
Kölker, S;Pawlak, V;Köhr, G
通讯作者：
Köhr, G