Chen Yan, Qi Shan-Shan, Ding Li-Li, DU Yu, Song Na, Wang Zhuo, Yang Li, Sun Ming, Xiong Hao
Laboratory of Pediatric Hematology， Wuhan Children's Hospital， Tongji Medical College， Huazhong University of Science ＆ Technology, Wuhan 430016， Hubei Province， China.
Department of Hematology and Oncology， Wuhan Children's Hospital， Tongji Medical College， Huazhong University of Science ＆ Technology, Wuhan 430016， Hubei Province， China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2023 Feb;31(1):17-24. doi: 10.19746/j.cnki.issn.1009-2137.2023.01.003.
To analyze the gene mutation profile in children with acute lymphocyte leukemia (ALL) and to explore its prognostic significance.
Clinical data of 249 primary pediatric ALL patients diagnosed and treated in the Department of Hematological Oncology of Wuhan Children's Hospital from January 2018 to December 2021 were analyzed retrospectively. Next-generation sequencing (NGS) was used to obtain gene mutation data and analyze the correlation between it and the prognosis of children with ALL.
227 (91.2%) were B-ALL, 22 (8.8%) were T-ALL among the 249 cases, and 178 (71.5%) were found to have gene mutations, of which 85 (34.1%) had ≥3 gene mutations. NRAS(23.7%), KRAS (22.9%),FLT3(11.2%), PTPN11(8.8%), CREBBP (7.2%), (6.4%) were the most frequently mutated genes, the mutations of KRAS, FLT3, PTPN11, CREBBP were mainly found in B-ALL, the mutations of and FBXW7 were mainly found in T-ALL. The gene mutation incidence of T-ALL was significantly higher than that of B-ALL (χ= 5.573，＜0.05) and were more likely to have co-mutations (＜0.05). The predicted 4-year EFS rate (47.9% vs 88.5%, ＜0.001) and OS rate (53.8% vs 94.1%, ＜0.001) in children with mutations were significantly lower than those of patients without mutations. Patients with mutations had higher initial white blood cell count （128.64×10/L vs 8.23×10/L，＜0.001）, and children with mutations had a lower 4-year EFS rate than those of without mutations (71.5% vs 87.2%, P＝0.037).
Genetic mutations are prevalent in childhood ALL and mutations in and are strong predictors of adverse outcomes in childhood ALL, with NGS contributing to the discovery of genetic mutations and timely adjustment of treatment regimens.
分析急性淋巴细胞白血病（ALL）患儿的基因突变谱，并探讨其预后意义。
回顾性分析2018年1月至2021年12月在武汉市儿童医院血液肿瘤科诊治的249例原发性小儿ALL患者的临床资料。采用二代测序（NGS）获取基因突变数据，并分析其与ALL患儿预后的相关性。
249例病例中，227例（91.2%）为B-ALL，22例（8.8%）为T-ALL，178例（71.5%）存在基因突变，其中85例（34.1%）有≥3个基因突变。NRAS（23.7%）、KRAS（22.9%）、FLT3（11.2%）、PTPN11（8.8%）、CREBBP（7.2%）、（6.4%）是最常发生突变的基因，KRAS、FLT3、PTPN11、CREBBP的突变主要见于B-ALL，和FBXW7的突变主要见于T-ALL。T-ALL的基因突变发生率显著高于B-ALL（χ=5.573，＜0.05），且更易发生共突变（＜0.05）。有突变的患儿预测4年无事件生存率（EFS）率（47.9%对88.5%，＜0.001）和总生存率（OS）率（53.8%对94.1%，＜0.001）显著低于无突变患者。有突变的患者初始白细胞计数较高（128.64×10/L对8.23×10/L，＜0.001），有突变的患儿4年EFS率低于无突变者（71.5%对87.2%，P＝0.037）。
基因突变在儿童ALL中普遍存在，和的突变是儿童ALL不良预后的有力预测指标，NGS有助于发现基因突变并及时调整治疗方案。
