State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University (SJTU) School of Medicine, Shanghai, China.
Int J Lab Hematol. 2018 Aug;40(4):408-418. doi: 10.1111/ijlh.12802. Epub 2018 Mar 24.
Cytogenetically normal acute myeloid leukemia (CN-AML), which accounted for nearly half of total AML patients, is a highly heterogeneous subset of AML. The specific genetic profile and the ethnic features of CN-AML are worth to be studied.
Using deep sequencing technology, we detected the mutation pattern of 39 genes in 152 Chinese CN-AML patients and analyzed their clinical features.
A total of 503 mutations of 39 genes were identified in 145 (95.4%) patients, with the median number of 3 mutations per case. Nine genes (NPM1, CEBPA, DNMT3A, GATA2, NRAS, TET2, FLT3, IDH2, and WT1) mutated in more than 10% patients. Function groups of myeloid transcription factors, activated signaling, and DNA methylation were most affected. The distribution of variant allele frequencies (VAF) of recurrent genes was different among functional groups. High mutation rates of CEBPA and GATA2 together with the low frequency of FLT3-ITD mutation seemed to be the distinct characteristics of Chinese patients. Furthermore, CEBPAbi and GATA2 were found to mutate most in M2 subtype, while NPM1 and DNMT3A mutated more in M4 and M5. The prognostic analysis identified CEBPAmo mutation as an inferior factor. FLT3-ITD, TP53, DNMT3A, CEBPAmo, and WT1 mutations were selected as high-risk markers to identify the CN-AML patients with poor prognosis.
Our study provided the valuable information of ethnic genetic characteristics and the clinical relevance of Chinese CN-AML patients.
核型正常的急性髓系白血病（CN-AML）占全部 AML 患者的近一半，是 AML 中高度异质性的亚群。CN-AML 的特定遗传特征和种族特征值得研究。
使用深度测序技术，我们检测了 152 例中国 CN-AML 患者 39 个基因的突变模式，并分析了它们的临床特征。
在 145 例（95.4%）患者中发现了 39 个基因的 503 个突变，中位数为每个病例 3 个突变。9 个基因（NPM1、CEBPA、DNMT3A、GATA2、NRAS、TET2、FLT3、IDH2 和 WT1）在超过 10%的患者中发生突变。受影响最大的功能群为髓系转录因子、激活信号和 DNA 甲基化。常见基因的变异等位基因频率（VAF）分布在不同的功能群之间。CEBPA 和 GATA2 的高突变率以及 FLT3-ITD 突变的低频率似乎是中国患者的独特特征。此外，CEBPAbi 和 GATA2 主要在 M2 亚型中突变，而 NPM1 和 DNMT3A 在 M4 和 M5 中突变更多。预后分析发现 CEBPAmo 突变是一个不利因素。FLT3-ITD、TP53、DNMT3A、CEBPAmo 和 WT1 突变被选为高风险标志物，以确定 CN-AML 患者的预后不良。
本研究提供了中国 CN-AML 患者的宝贵种族遗传特征和临床相关性信息。
