Distinct clinical and biologic characteristics in adult acute myeloid leukemia bearing the isocitrate dehydrogenase 1 mutation
Distinct clinical and biologic characteristics in adult acute myeloid leukemia bearing the isocitrate dehydrogenase 1 mutation
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DOI：
10.1182/blood-2009-11-253070
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发表时间：
2010-04-08
期刊：
影响因子：
20.3
通讯作者：
Tien, Hwei-Fang
中科院分区：
文献类型：
--
作者：
Chou, Wen-Chien;Hou, Hsin-An;Tien, Hwei-Fang
已在神经胶质瘤患者中鉴定出烟酰胺腺嘌呤二核苷酸磷酸依赖性异柠檬酸脱氢酶基因（IDH 1）突变。最近的全基因组筛查也显示IDH 1突变是急性髓细胞白血病（AML）的复发事件，但其在AML中的临床意义在很大程度上是未知的。我们分析了493例中国台湾成人AML患者，发现27例患者（5.5%）携带这种突变。IDH 1突变与正常核型密切相关（8.4%，P = .002），孤立的单体性8（P = .043），NPM 1突变（P < .001），法国-美国-英国M1亚型（P < .001），但与法国-美国-英国M4亚型呈负相关（P = 0.030）和HLA-DR、CD 13和CD 14的表达（分别为P = 0.002、0.003和0.038）。这种突变对患者生存率没有影响。对130例随访患者进行IDH 1突变的序列分析。112例在诊断时没有IDH 1突变的患者在复发时没有获得这种突变。在研究的所有18名IDH 1突变患者中，突变在完全缓解时消失;在复发时获得的所有11个样本中再次出现相同的突变。我们的结论是IDH 1与独特的临床和生物学特征相关，并且在疾病演变过程中似乎非常稳定。（血。2010; 115（14）：2749-2754）
Mutations of nicotinamide adenine dinucleotide phosphate-dependent isocitrate dehydrogenase gene (IDH1) have been identified in patients with gliomas. Recent genome-wide screening also revealed IDH1 mutation as a recurrent event in acute myeloid leukemia (AML), but its clinical implications in AML are largely unknown. We analyzed 493 adult Chinese AML patients in Taiwan and found 27 patients (5.5%) harboring this mutation. IDH1 mutation was strongly associated with normal karyotype (8.4%, P = .002), isolated monosomy 8 (P = .043), NPM1 mutation (P < .001), and French-American-British M1 subtype (P < .001), but inversely associated with French-American-British M4 subtype (P = .030) and expression of HLA-DR, CD13, and CD14 (P = .002, .003, and .038, respectively). There was no impact of this mutation on patient survival. Sequential analysis of IDH1 mutation was performed in 130 patients during follow-ups. None of the 112 patients without IDH1 mutation at diagnosis acquired this mutation at relapse. In all 18 IDH1-mutated patients studied, the mutation disappeared in complete remission; the same mutation reappeared in all 11 samples obtained at relapse. We conclude that IDH1 is associated with distinct clinical and biologic characteristics and seems to be very stable during disease evolution. (Blood. 2010; 115(14): 2749-2754)