Ma Juan, Dunlap Jennifer, Paliga Aleksandra, Traer Elie, Press Richard, Shen Lisong, Fan Guang
a Department of Clinical Laboratory , Xinhua Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , PR China.
b Department of Pathology and Laboratory Medicine , Oregon Health & Science University , Portland , OR , USA.
Leuk Lymphoma. 2018 Aug;59(8):1938-1948. doi: 10.1080/10428194.2017.1397659. Epub 2017 Nov 22.
This single institution cohort study of 132 AML patients investigated the clinical implications of co-mutations detected with a 42-gene NGS panel. In the intermediate-risk cytogenetic group, FLT3-ITD is an adverse prognostic indicator only in the presence of a DNMT3A co-mutation, regardless of NPM1 mutation status. In the absence of a concomitant DNMT3A mutation, there was no significant difference in overall survival between FLT3-ITD positive and FLT3-ITD negative patients. Furthermore, mutation analysis on post-induction specimens showed that residual FLT3-ITD and/or DNMT3A mutations were associated with a high frequency of therapy resistance or relapse in AML. While FLT3-ITD positive patients are currently considered high risk, incorporation of DNMT3A mutation status may be needed to refine prognostication and guide clinical management in AML. Multi-gene mutation testing is essential to provide novel insights related to diagnostic and prognostic information.
这项针对132例急性髓系白血病（AML）患者的单机构队列研究，调查了通过42基因二代测序（NGS） panel检测到的共突变的临床意义。在中危细胞遗传学组中，FLT3内部串联重复（FLT3-ITD）仅在存在DNMT3A共突变时才是不良预后指标，与NPM1突变状态无关。在没有伴随DNMT3A突变的情况下，FLT3-ITD阳性和FLT3-ITD阴性患者的总生存期无显著差异。此外，诱导后标本的突变分析表明，残留的FLT3-ITD和/或DNMT3A突变与AML治疗耐药或复发的高频率相关。虽然目前FLT3-ITD阳性患者被视为高危，但可能需要纳入DNMT3A突变状态以完善AML的预后评估并指导临床管理。多基因突变检测对于提供与诊断和预后信息相关的新见解至关重要。
