文章：

FLT3-ITD 的定量片段分析可有效识别具有高突变等位基因负荷或长 ITD 长度的预后不良组

Quantitative fragment analysis of FLT3-ITD efficiently identifying poor prognostic group with high mutant allele burden or long ITD length

原文发布日期：2015-08-14

DOI: 10.1038/bcj.2015.61

类型: Original Article

开放获取: 是

英文摘要：

Mutation of the fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD), which is one of the most frequent genetic alterations, strongly contributes to an increased risk of treatment failure and to poor prognosis. In this study, we established quantitative fragment analysis of FLT3-ITD simultaneously measuring mutant allele burden and length, verified the analytical performance and evaluated the clinical significance in adult acute myeloid leukemia (AML) patients. FLT3-ITD was detected in 73 of 363 adult AML patients (20.1%) and high mutant allelic burden (⩾50%, n=13) and long ITD length (⩾70 base pairs, n=15) were significantly associated with inferior overall survival (OS; P=0.002 and 0.005, respectively) and event-free survival (EFS; P=0.004 and 0.007, respectively). FLT3-ITD poor prognostic group was identified as patients with high allele burden or long ITD length (n=24), which revealed significant adverse clinical outcome for both OS (P<0.001) and EFS (P<0.001). In cytogenetically normal AML, even FLT3-ITD low allele burden and short length was associated with poorer OS (P=0.037) and EFS (P=0.044) than wild type, whose influence was overcome when hematopoietic stem cell transplantation was performed. In minimal residual disease monitoring, FLT3-ITD negativity after consolidation therapy was a valuable predictor of better OS (P<0.001) and EFS (P<0.001). FLT3-ITD poor prognostic group with high mutant allele burden or long ITD length is efficiently identified by quantitative fragment analysis.

摘要翻译： 

fms样酪氨酸激酶3内部串联重复（FLT3-ITD）突变作为最常见的遗传学改变之一，会显著增加治疗失败风险并导致不良预后。本研究建立了同步检测突变等位基因负荷与片段长度的FLT3-ITD定量片段分析法，验证了其分析性能，并评估其在成人急性髓系白血病（AML）患者中的临床意义。在363例成人AML患者中，73例（20.1%）检出FLT3-ITD，其中高突变等位基因负荷（⩾50%，n=13）和长ITD片段（⩾70碱基对，n=15）与较差的总生存期（OS；P值分别为0.002和0.005）及无事件生存期（EFS；P值分别为0.004和0.007）显著相关。FLT3-ITD不良预后组（即具有高等位基因负荷或长ITD片段的患者，n=24）在OS（P<0.001）和EFS（P<0.001）方面均呈现显著不利临床结局。在细胞遗传学正常的AML中，即便是低等位基因负荷和短片段的FLT3-ITD，其OS（P=0.037）和EFS（P=0.044）也差于野生型，但这种不利影响在实施造血干细胞移植后被克服。在微小残留病监测中，巩固治疗后FLT3-ITD转阴是预测更好OS（P<0.001）和EFS（P<0.001）的重要指标。通过定量片段分析法可有效识别具有高突变等位基因负荷或长ITD片段的FLT3-ITD不良预后组。

原文链接：

Quantitative fragment analysis of FLT3-ITD efficiently identifying poor prognostic group with high mutant allele burden or long ITD length