IDH1 and IDH2 mutations confer an adverse effect in patients with acute myeloid leukemia lacking the NPM1 mutation
IDH1 and IDH2 mutations confer an adverse effect in patients with acute myeloid leukemia lacking the NPM1 mutation
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DOI：
10.1111/ejh.12271
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发表时间：
2014-06
影响因子：
3.1
通讯作者：
Shunichiro Yamaguchi;Eisaku Iwanaga;K. Tokunaga;T. Nanri;T. Shimomura;H. Suzushima;H. Mitsuya;N. Asou
中科院分区：
文献类型：
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作者：
Shunichiro Yamaguchi;Eisaku Iwanaga;K. Tokunaga;T. Nanri;T. Shimomura;H. Suzushima;H. Mitsuya;N. Asou
我们研究了233例日本成人急性髓性白血病（AML）患者IDH1和IDH2突变的发生率和预后影响。在20例（8.6%）AML患者中检测到IDH1 R132突变。IDH2突变在19例（8.2%，17例R140和2例R172）患者中发现。IDH1和IDH2突变相互排斥，与正常核型AML、细胞遗传学中危组和NPM1突变相关。在整个AML队列中，携带IDH突变的患者的5年总生存率（OS）（15.6%）显著低于缺乏IDH突变的患者（32.0%）（P = 0.005）。在年龄小于等于59岁的IDH突变患者中，接受异基因干细胞移植（SCT）的患者的5年OS显著高于未接受异基因SCT的患者（50% vs. 10.6%，P = 0.020）。在51例NPM1突变患者中，IDH突变患者和非IDH突变患者的5年OS率无显著差异。相比之下，在175名缺乏NPM 1突变的患者中，有IDH突变的患者的5年OS率明显低于无IDH突变的患者（0%比34.7%，P = <0.001）。这些数据表明，IDH突变对AML有不利影响，尤其是NPM 1野生型AML，IDH突变的年轻AML患者可能受益于同种异体SCT。
We examined the incidence and prognostic effect of IDH1 and IDH2 mutations in 233 Japanese adults with acute myeloid leukemia (AML). IDH1 R132 mutations were detected in 20 (8.6%) patients with AML. IDH2 mutations were found in 19 (8.2%, 17 R140 and two R172) patients. IDH1 and IDH2 mutations were mutually exclusive and were associated with normal karyotype AML, cytogenetic intermediate‐risk group, and NPM1 mutations. Five‐year overall survival (OS) rates were significantly lower (15.6%) in patients harboring the IDH mutations than in patients lacking the IDH mutation (32.0%) in the entire cohort of AML (P = 0.005). Among patients aged 59 yr or younger with IDH mutations, 5‐yr OS in patients who underwent allogeneic stem cell transplantation (SCT) was significantly higher than that in those not receiving allogeneic SCT (50% vs. 10.6%, P = 0.020). Of 51 patients with NPM1 mutations, there was no significant difference in 5‐yr OS rates between patients with and those without the IDH mutations. In contrast, among 175 patients lacking the NPM1 mutations, 5‐yr OS rate in patients with IDH mutations was significantly lower than that in those without IDH mutations (0% vs. 34.7%, P = <0.001). These data suggest that IDH mutations have an unfavorable effect in AML, especially AML with the NPM1 wild type and younger AML patients with IDH mutations may benefit from allogeneic SCT.