文章：

KIT 17号外显子突变的意义在核心结合因子急性髓系白血病中取决于突变水平而非是否阳性

Significance of KIT exon 17 mutation depends on mutant level rather than positivity in core-binding factor acute myeloid leukemia

原文发布日期：2016-01-15

DOI: 10.1038/bcj.2015.116

类型: Original Article

开放获取: 是

英文摘要：

KIT exon 17 mutation is a poor prognostic factor in core-binding factor acute myeloid leukemia. However, the mutation detection method used for risk assessment is not assigned. It is necessary to verify the analytical and clinical performance before applying new methods. Herein, we firstly applied a highly sensitive allele-specific, real-time quantitative PCR (AS-qPCR) assay to analyze KIT mutations, which demonstrated excellent sensitivity and specificity. Much higher incidence of KIT mutations (62.2%, 69/111) and prevalence of multiple mutations (43.5%, 30/69) were observed using AS-qPCR, which meant the existence of multiple KIT mutant subclones. The relative KIT mutant level was variable (median, 0.3 per control allele 100 copies, 0.002–532.7) and was divided into two groups: high (⩾10, n=26) and low (<10) mutant level. Interestingly, rather than mutation positivity, mutant level was found to be associated with clinical outcome. High mutant level showed significantly inferior overall survival (P=0.005) and event-free survival (P=0.03), whereas low level did not influence the prognosis. The follow-up data showed that the mutant level were along with fusion transcripts in the majority (n=29), but moved separately in some cases, including the loss of mutations (n=5) and selective proliferation of minor clones (n=2) at relapse. This study highlighted that the KIT mutation should be analyzed using sensitive and quantitative techniques and set a cutoff level for identifying the risk group.

摘要翻译： 

KIT外显子17突变是核心结合因子急性髓系白血病的不良预后因素。然而，目前用于风险评估的突变检测方法尚未统一标准。在应用新方法前，有必要验证其分析性能与临床效能。本研究首次采用高灵敏度等位基因特异性实时定量PCR（AS-qPCR）技术检测KIT突变，该方法展现出卓越的灵敏度与特异性。通过AS-qPCR检测发现KIT突变发生率显著升高（62.2%，69/111），且多重突变发生率高（43.5%，30/69），提示存在多个KIT突变亚克隆。KIT相对突变水平存在较大差异（中位数0.3/100个对照等位基因拷贝，范围0.002-532.7），可分为高突变水平组（⩾10，n=26）和低突变水平组（<10）。值得注意的是，与突变阳性本身相比，突变水平与临床结局更具相关性。高突变水平组患者总生存期（P=0.005）和无事件生存期（P=0.03）显著缩短，而低突变水平则不影响预后。随访数据显示，多数病例（n=29）突变水平与融合转录本变化趋势一致，但部分病例出现异常：包括复发时突变丢失（n=5）及次要克隆选择性增殖（n=2）。本研究强调应采用灵敏定量技术分析KIT突变，并设立临界值以识别风险人群。

原文链接：

Significance of KIT exon 17 mutation depends on mutant level rather than positivity in core-binding factor acute myeloid leukemia