The prognostic impact and stability of Isocitrate dehydrogenase 2 mutation in adult patients with acute myeloid leukemia
The prognostic impact and stability of Isocitrate dehydrogenase 2 mutation in adult patients with acute myeloid leukemia
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DOI：
10.1038/leu.2010.267
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发表时间：
2011-02-01
期刊：
影响因子：
11.4
通讯作者：
Tien, H-F
中科院分区：
文献类型：
--
作者：
Chou, W-C;Lei, W-C;Tien, H-F
虽然异柠檬酸脱氢酶2（IDH 2）突变在急性髓细胞白血病（AML）的临床特征已被表征，其预后意义仍然存在争议，其稳定性尚未进行研究。我们分析了446名患有原发性非M3 AML的成年人，发现IDH 2 R172、R140和IDH 1 R132突变的发生频率分别为2.9%、9.2%和6.1%。与野生型IDH 2相比，IDH 2突变与血小板计数升高、中危或正常核型及孤立+8相关，但与HLA-DR、CD 34、CD 15、CD 7和CD 56表达呈负相关，与WT 1突变和涉及核心结合因子的染色体易位相互排斥。当IDH 1和IDH 2突变一起考虑时，所有这些相关性变得更强。多因素分析显示IDH 2突变是独立的有利预后因素。IDH 2（-）/FLT 3-ITD+基因型对生存率的影响尤其不利。与IDH 2 R140突变相比，IDH 2 R172突变与年龄、白色细胞计数和乳酸脱氢酶水平降低相关，与NPM 1突变相互排斥。对121例患者诊断和复发时IDH 2突变的系列分析证实了IDH 2突变的高稳定性。总之，IDH 2突变是疾病演变过程中的稳定标志物，并赋予良好的预后。Leukemia（2011）25，246-253; doi：10.1038/leu.2010.267; 2010年11月16日在线发表
Although the clinical features of the Isocitrate dehydrogenase 2 (IDH2) mutation in acute myeloid leukemia (AML) have been characterized, its prognostic significance remains controversial and its stability has not been investigated. We analyzed 446 adults with primary non-M3 AML and found IDH2 R172, R140 and IDH1 R132 mutations occurred at a frequency of 2.9, 9.2 and 6.1%, respectively. Compared with wild-type IDH2, mutation of IDH2 was associated with higher platelet counts, intermediate-risk or normal karyotype and isolated +8, but was inversely correlated with expression of HLA-DR, CD34, CD15, CD7 and CD56, and was mutually exclusive with WT1 mutation and chromosomal translocations involving core-binding factors. All these correlations became stronger when IDH1 and IDH2 mutations were considered together. Multivariate analysis revealed IDH2 mutation as an independent favorable prognostic factor. IDH2(-)/FLT3-ITD+ genotype conferred especially negative impact on survival. Compared with IDH2 R140 mutation, IDH2 R172 mutation was associated with younger age, lower white blood cell count and lactate dehydrogenase level, and was mutually exclusive with NPM1 mutation. Serial analyses of IDH2 mutations at both diagnosis and relapse in 121 patients confirmed high stability of IDH2 mutations. In conclusion, IDH2 mutation is a stable marker during disease evolution and confers favorable prognosis. Leukemia (2011) 25, 246-253; doi:10.1038/leu.2010.267; published online 16 November 2010