Department of Pathology, Queen Elizabeth Hospital, Hong Kong, China.
School of Biomedical Sciences, The University of Western Australia, Perth, WA, Australia.
Cancer Rep (Hoboken). 2022 Oct;5(10):e1573. doi: 10.1002/cnr2.1573. Epub 2021 Oct 6.
Acute myeloid leukaemia (AML) results from the clonal expansion of blast cells of myeloid origin driven by genomic defects. The advances in next-generation sequencing (NGS) have allowed the identification of many mutated genes important in the pathogenesis of AML.
In this study, we aimed to assess the mutation types and frequency in a Chinese cohort presenting with de novo AML cohort using a targeted NGS strategy.
In total, we studied samples from 87 adult patients with de novo AML who had no prior history of cytotoxic chemotherapy. Samples were evaluated using a 120-gene targeted NGS panel to assess the mutation profile.
Of the 87 AML patients, there were 60 (69%) with a normal karyotype. 89.7% of patients had variants, with an average of 1.9 mutations per patient (range: 0-5 mutations per patient). DNMT3A variants were the most common, being detected in 33 patients (37.9%). NPM1 (34.5%), IDH1/2 (24.1%) and FLT3-ITD (20.7%) mutations was the next most common. Of the patients with DNMT3A mutations, 24.2% also had mutations NPM1 and FLT3-ITD and 6.1% NPM1, FLT3-ITD and IDH mutations.
Both DNMT3A and NPM1 mutations were more common than in other Chinese and Western AML cohorts that have been studied. DNMT3A mutations tended to co-occur with NPM1 and FLT3-ITD mutations and were most commonly seen with a normal karyotype.
急性髓系白血病（AML）是由髓系起源的原始细胞克隆性扩增引起的，其发病机制与基因组缺陷有关。下一代测序（NGS）技术的进步使得许多在 AML 发病机制中起重要作用的突变基因得以鉴定。
本研究旨在采用靶向 NGS 策略，评估中国初诊 AML 患者的突变类型和频率。
共研究了 87 例无既往细胞毒性化疗史的初诊 AML 成年患者的样本。采用 120 基因靶向 NGS panel 评估突变谱。
在 87 例 AML 患者中，有 60 例（69%）核型正常。89.7%的患者有变异，平均每位患者有 1.9 个突变（范围：每位患者 0-5 个突变）。DNMT3A 变异最为常见，共 33 例（37.9%）。NPM1（34.5%）、IDH1/2（24.1%）和 FLT3-ITD（20.7%）突变次之。DNMT3A 突变患者中有 24.2%还存在 NPM1 和 FLT3-ITD 突变，6.1%存在 NPM1、FLT3-ITD 和 IDH 突变。
DNMT3A 和 NPM1 突变在中国和西方 AML 患者中比其他研究更为常见。DNMT3A 突变常与 NPM1 和 FLT3-ITD 突变共存，且最常见于核型正常的患者。
