High IDH1 expression is associated with a poor prognosis in cytogenetically normal acute myeloid leukemia
High IDH1 expression is associated with a poor prognosis in cytogenetically normal acute myeloid leukemia
复制标题
IDH1 高表达与细胞遗传学正常急性髓系白血病的不良预后相关
DOI：
10.1002/ijc.29395
复制
发表时间：
2015-09-01
影响因子：
6.4
通讯作者：
Jin, Jie
中科院分区：
文献类型：
--
作者：
Ma, Qiu-Ling;Wang, Jing-Han;Jin, Jie
IDH 1基因突变对急性髓系白血病（AML）患者预后的价值已被系统评估。然而，IDH 1表达在AML中的作用仍在探索中。为探讨IDH 1/2的临床意义，我们采用定量真实的时间逆转录聚合酶链反应（RT-PCR）分析了320例细胞遗传学正常的AML（CN‐AML）患者IDH 1/2的表达。IDH 1的高表达在FLT 3-ITD和DNMT 3A突变患者中占主导地位，在CEBPA双等位基因突变病例中不太常见。IDH 1高表达与microRNA 181家族低表达之间存在强相关性。预后受到IDH 1高表达的不利影响，在临床特征（包括年龄、WBC计数和CN-AML中NPM 1、FLT 3-ITD、CEBPA、IDH 1、IDH 2和DNMT 3A的基因突变）的背景下，总生存期和无事件生存期较短。此外，IDH 1表达在总生存期、无事件生存期和完全缓解率方面的临床结局仍然存在于CN-AML的多变量模型中。重要的是，使用根据德国AMLCG-1999方案治疗的79例成人患者的已发表微阵列数据验证了预后价值。我们的研究结果表明，IDH 1高表达与CN-AML的预后不良相关。
The prognostic value of IDH1 mutations has been systematically evaluated in acute myeloid leukemia (AML) patients recently. However, the role of IDH1 expression in AML is still under exploration. To investigate the clinical significance, we analyzed the IDH1/2 expression in 320 patients with cytogenetically normal AML (CN‐AML) by quantitative real‐time reverse‐transcription polymerase chain reaction. High expression of IDH1 was predominant in patients with FLT3‐ITD and DNMT3A mutations and less prevalent in cases with CEBPA double allele mutations. Strong association was observed between high IDH1 expression and low expression of microRNA 181 family. Prognosis was adversely affected by high IDH1 expression, with shorter overall survival and event‐free survival in the context of clinical characteristics, including age, WBC count, and gene mutations of NPM1, FLT3‐ITD, CEBPA, IDH1, IDH2 and DNMT3A in CN‐AML. Moreover, the clinical outcome of IDH1 expression in terms of overall survival, event‐free survival and complete remission rate still remained in multivariate models in CN‐AML. Importantly, the prognostic value was validated using the published microarray data from 79 adult patients treated according to the German AMLCG‐1999 protocol. Our results demonstrated that high IDH1 expression is associated with a poor prognosis of CN‐AML.