Tan Marcus, Ng Isaac K S, Chen Zhaojin, Ban Kenneth, Ng Christopher, Chiu Lily, Seah Elaine, Lin Mingxuan, Tai Bee Choo, Yan Benedict, Ng Chin Hin, Chng Wee-Joo
Department of Biochemistry, National University of Singapore, Singapore, Singapore.
Investigational Medicine Unit, National University Health System, Singapore, Singapore.
J Clin Pathol. 2017 Aug;70(8):669-676. doi: 10.1136/jclinpath-2016-204195. Epub 2017 Jan 18.
In recent years, genomic technologies have enabled the identification of mutations in acute myeloid leukaemia (AML). is a recurrently mutated epigenetic modifier gene in AML. To date, the prognostic significance of mutations has not been studied in a Southeast Asian AML population. We sought to investigate the clinical implications of mutations in a Southeast Asian cohort of AML patients.
mutations were identified using a targeted next-generation sequencing panel in 157 AML patients. We studied the molecular and clinical features of patients with mutations and assessed the prognostic impact of mutations.
mutations were found in 33 of 157 (21.0%) AML patients. 114 patients were included for statistical analysis. Pretreatment data revealed that patients with mutations were older (≥60 years old), had a higher white blood cell count at diagnosis, had more adverse cytogenetic risk profiles and were more often associated with mutations compared with patients with wild-type . Survival analysis showed that DNMT3A mutations were associated with poorer clinical outcomes. This was especially when associated with NPM1 and FLT3-ITD mutations (AML ), which are common. The AML subtype was an independent predictor for poorer overall survival (OS). Other independent risk factors for poorer OS include advanced age at diagnosis and adverse cytogenetic risk stratification.
mutations are associated with an unfavourable clinical outcome in our Southeast Asian AML patient cohort. In particular, AML patients had the poorest prognosis.
近年来，基因组技术已能够识别急性髓系白血病（AML）中的突变。DNMT3A是AML中一个反复发生突变的表观遗传修饰基因。迄今为止，尚未在东南亚AML患者群体中研究DNMT3A突变的预后意义。我们试图在东南亚AML患者队列中研究DNMT3A突变的临床意义。
使用靶向二代测序panel在157例AML患者中鉴定DNMT3A突变。我们研究了DNMT3A突变患者的分子和临床特征，并评估了DNMT3A突变的预后影响。
在157例（21.0%）AML患者中的33例中发现了DNMT3A突变。114例患者纳入统计分析。预处理数据显示，与野生型DNMT3A患者相比，DNMT3A突变患者年龄较大（≥60岁），诊断时白细胞计数较高，细胞遗传学风险特征更差，且更常与NPM1突变相关。生存分析表明，DNMT3A突变与较差的临床结局相关。当与常见的NPM1和FLT3-ITD突变相关时尤其如此（AML伴DNMT3A、NPM1和FLT3-ITD突变）。AML伴DNMT3A、NPM1和FLT3-ITD突变亚型是总生存期（OS）较差的独立预测因素。其他OS较差的独立危险因素包括诊断时年龄较大和不良细胞遗传学风险分层。
在我们的东南亚AML患者队列中，DNMT3A突变与不良临床结局相关。特别是，AML伴DNMT3A、NPM1和FLT3-ITD突变患者预后最差。
