Mutations of Epigenetic Modifier Genes as a Poor Prognostic Factor in Acute Promyelocytic Leukemia Under Treatment With All-Trans Retinoic Acid and Arsenic Trioxide.
Mutations of Epigenetic Modifier Genes as a Poor Prognostic Factor in Acute Promyelocytic Leukemia Under Treatment With All-Trans Retinoic Acid and Arsenic Trioxide.
复制标题
表观遗传修饰基因突变是全反式视黄酸和三氧化二砷治疗急性早幼粒细胞白血病的不良预后因素。
DOI：
10.1016/j.ebiom.2015.04.006
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发表时间：
2015-06
期刊：
影响因子：
11.1
通讯作者：
Chen SJ
中科院分区：
文献类型：
--
作者：
Shen Y;Fu YK;Zhu YM;Lou YJ;Gu ZH;Shi JY;Chen B;Chen C;Zhu HH;Hu J;Zhao WL;Mi JQ;Chen L;Zhu HM;Shen ZX;Jin J;Wang ZY;Li JM;Chen Z;Chen SJ
急性早幼粒细胞白血病 (APL) 是使用全反式维甲酸 (ATRA) 和三氧化二砷 (ATO) 进行协同靶向癌症治疗的模型，可产生高达 85% 至 90% 的 5 年总生存率 (OS)。尽管如此，约15%的APL患者仍然过早死亡或复发。我们进行这项研究是为了解决额外基因突变对 APL 结果可能产生的影响。我们纳入了连续的266例病例作为训练组，然后在269例患者的测试组中验证结果，以调查潜在的预后基因突变，包括FLT3-ITD或-TKD、N-RAS、C-KIT、NPM1、CEPBA、WT1、ASXL1、DNMT3A、MLL（融合和PTD）、IDH1、IDH2和TET2。与中危和低危患者相比，更多高危患者（50.4%）携带额外突变。表观遗传修饰基因的突变与训练组（HR = 6.761，95% CI 2.179–20.984；P = 0.001）和验证组（HR = 4.026，95% CI 1.089–14.878；P = 0.037）的不良预后相关。 Sanz 风险分层与 CR 诱导和 OS 相关。在ATRA/ATO治疗时代，分子标志物和基于临床参数的分层系统都应作为APL的预后因素。 EMG 突变与 APL 不良预后相关。 Sanz 风险系统可用于预测 ATRA/ATO 治疗后的 CR 和 OS。
Acute promyelocytic leukemia (APL) is a model for synergistic target cancer therapy using all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), which yields a very high 5-year overall survival (OS) rate of 85 to 90%. Nevertheless, about 15% of APL patients still get early death or relapse. We performed this study to address the possible impact of additional gene mutations on the outcome of APL. We included a consecutive series of 266 cases as training group, and then validated the results in a testing group of 269 patients to investigate the potential prognostic gene mutations, including FLT3-ITD or -TKD, N-RAS, C-KIT, NPM1, CEPBA, WT1, ASXL1, DNMT3A, MLL (fusions and PTD), IDH1, IDH2 and TET2. More high-risk patients (50.4%) carried additional mutations, as compared with intermediate- and low-risk ones. The mutations of epigenetic modifier genes were associated with poor prognosis in terms of disease-free survival in both training (HR = 6.761, 95% CI 2.179–20.984; P = 0.001) and validation (HR = 4.026, 95% CI 1.089–14.878; P = 0.037) groups. Sanz risk stratification was associated with CR induction and OS. In an era of ATRA/ATO treatment, both molecular markers and clinical parameter based stratification systems should be used as prognostic factors for APL. The EMG mutations were associated with poor prognosis in APL. Sanz risk system was useful to predict the CR and OS upon ATRA/ATO treatment.