文章：

在核心结合因子急性髓系白血病中，采用髓系基因进行下一代测序发现 KIT 激活环和 TET2 突变可预测预后

Next-generation sequencing with a myeloid gene panel in core-binding factor AML showed KIT activation loop and TET2 mutations predictive of outcome

原文发布日期：2016-07-08

DOI: 10.1038/bcj.2016.51

类型: Original Article

开放获取: 是

英文摘要：

Clinical outcome and mutations of 96 core-binding factor acute myeloid leukemia (AML) patients 18–60 years old were examined. Complete remission (CR) after induction was 94.6%. There was no significant difference in CR, leukemia-free-survival (LFS) and overall survival (OS) between t(8;21) (N=67) and inv(16) patients (N=29). Univariate analysis showed hematopoietic stem cell transplantation at CR1 as the only clinical parameter associated with superior LFS. Next-generation sequencing based on a myeloid gene panel was performed in 72 patients. Mutations in genes involved in cell signaling were associated with inferior LFS and OS, whereas those in genes involved in DNA methylation were associated with inferior LFS. KIT activation loop (AL) mutations occurred in 25 patients, and were associated with inferior LFS (P=0.003) and OS (P=0.001). TET2 mutations occurred in 8 patients, and were associated with significantly shorter LFS (P=0.015) but not OS. Patients negative for KIT-AL and TET2 mutations (N=41) had significantly better LFS (P<0.001) and OS (P=0.012) than those positive for both or either mutation. Multivariate analysis showed that KIT-AL and TET2 mutations were associated with inferior LFS, whereas age ⩾40 years and marrow blast ⩾70% were associated with inferior OS. These observations provide new insights that may guide better treatment for this AML subtype.

摘要翻译： 

本研究对96例18-60岁核心结合因子急性髓系白血病（AML）患者的临床结局及基因突变进行了分析。诱导治疗后完全缓解（CR）率为94.6%。t(8;21)（67例）与inv(16)（29例）患者在CR率、无白血病生存（LFS）和总生存（OS）方面均无显著差异。单因素分析显示，首次完全缓解期行造血干细胞移植是改善LFS的唯一临床因素。基于髓系基因组的二代测序在72例患者中开展，结果显示：细胞信号传导相关基因突变与较差LFS及OS相关，而DNA甲基化相关基因突变仅与较差LFS相关。25例患者存在KIT激活环（AL）突变，该突变与较差LFS（P=0.003）和OS（P=0.001）显著相关；8例患者存在TET2突变，该突变与LFS显著缩短相关（P=0.015），但与OS无显著关联。KIT-AL与TET2双阴性患者（41例）的LFS（P<0.001）和OS（P=0.012）均显著优于单突变或双突变阳性患者。多因素分析表明，KIT-AL与TET2突变是LFS的独立不良预后因素，而年龄≥40岁及骨髓原始细胞≥70%是OS的独立不良预后因素。这些发现为指导该AML亚型的精准治疗提供了新见解。

原文链接：

Next-generation sequencing with a myeloid gene panel in core-binding factor AML showed KIT activation loop and TET2 mutations predictive of outcome