Gene mutation patterns in patients with minimally differentiated acute myeloid leukemia.
Gene mutation patterns in patients with minimally differentiated acute myeloid leukemia.
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DOI：
10.1016/j.neo.2014.06.002
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发表时间：
2014-06
期刊：
影响因子：
4.8
通讯作者：
Shih, Lee-Yung
中科院分区：
文献类型：
--
作者：
Kao, Hsiao-Wen;Liang, Der-Cherng;Wu, Jin-Hou;Kuo, Ming-Chung;Wang, Po-Nan;Yang, Chao-Ping;Shih, Yu-Shu;Lin, Tung-Huei;Huang, Yu-Hui;Shih, Lee-Yung
急性髓细胞白血病（AML）是一种罕见的急性髓细胞白血病亚型，预后差。尽管AML中的基因改变报道越来越多，但在AML-M0中尚未对基因突变进行全面研究。我们的目的是检查AML-M0患者的广泛基因突变，以确定其临床相关性。在67例AML-M0患者中分析了20种基因突变，包括表观遗传调节因子的I类、II类、III类（IDH 1、IDH 2、TET 2、DNMT 3A、MLL-PTD、ASXL 1和EZH 2）和IV类（肿瘤抑制基因）。采用基于聚合酶链反应的测定法进行突变分析，然后进行直接测序。我们数据中最常见的基因突变是FLT 3-ITD/FLT 3-TKD（28.4%），其次是IDH 1/IDH 2（28.8%）、RUNX 1（23.9%）、N-RAS/K-RAS（12.3%）、TET 2（8.2%）、DNMT 3A（8.1%）、MLL-PTD（7.8%）和ASXL 1（6.3%）突变。79%（53/67）的患者至少有一个基因突变。I类基因（49.3%）是最常见的突变基因，它们是互斥的。表观遗传调节因子III类基因也很常见（43.9%）。在多变量分析中，高龄[风险比（HR）1.029，95%置信区间（CI）1.013-1.044，P = .001）是总生存期的独立不利因素，RUNX 1突变（HR 2.326，95% CI 0.978-5.533，P = .056）有生存期较差的趋势。总之，我们的研究表明，在AML-M0中FLT 3、RUNX 1和IDH突变的频率很高，这表明这些突变在发病机制中起作用，并在这种罕见且不利的AML亚型中作为潜在的治疗靶点。
Minimally differentiated acute myeloid leukemia (AML-M0) is a rare subtype of AML with poor prognosis. Although genetic alterations are increasingly reported in AML, the gene mutations have not been comprehensively studied in AML-M0. We aimed to examine a wide spectrum of gene mutations in patients with AML-M0 to determine their clinical relevance. Twenty gene mutations including class I, class II, class III of epigenetic regulators (IDH1, IDH2, TET2, DNMT3A, MLL-PTD, ASXL1, and EZH2), and class IV (tumor suppressor genes) were analyzed in 67 patients with AML-M0. Mutational analysis was performed with polymerase chain reaction–based assays followed by direct sequencing. The most frequent gene mutations from our data were FLT3-ITD/FLT3-TKD (28.4%), followed by mutations in IDH1/IDH2 (28.8%), RUNX1 (23.9%), N-RAS/K-RAS (12.3%), TET2 (8.2%), DNMT3A (8.1%), MLL-PTD (7.8%), and ASXL1 (6.3%). Seventy-nine percent (53/67) of patients had at least one gene mutation. Class I genes (49.3%) were the most common mutated genes, which were mutually exclusive. Class III genes of epigenetic regulators were also frequent (43.9%). In multivariate analysis, old age [hazard ratio (HR) 1.029, 95% confidence interval (CI) 1.013-1.044, P = .001) was the independent adverse factor for overall survival, and RUNX1 mutation (HR 2.326, 95% CI 0.978-5.533, P = .056) had a trend toward inferior survival. In conclusion, our study showed a high frequency of FLT3, RUNX1, and IDH mutations in AML-M0, suggesting that these mutations played a role in the pathogenesis and served as potential therapeutic targets in this rare and unfavorable subtype of AML.
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