Objective: To analyze the gene mutation profile in children with acute lymphocyte leukemia (ALL) and to explore its prognostic significance.
Methods: 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.
Results: 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%), NOTCH1(6.4%) were the most frequently mutated genes, the mutations of KRAS, FLT3, PTPN11, CREBBP were mainly found in B-ALL, the mutations of NOTCH1 and FBXW7 were mainly found in T-ALL. The gene mutation incidence of T-ALL was significantly higher than that of B-ALL (χ2= 5.573，P＜0.05) and were more likely to have co-mutations (P＜0.05). The predicted 4-year EFS rate (47.9% vs 88.5%, P＜0.001) and OS rate (53.8% vs 94.1%, P＜0.001) in children with tp53 mutations were significantly lower than those of patients without tp53 mutations. Patients with NOTCH1 mutations had higher initial white blood cell count （128.64×109/L vs 8.23×109/L，P＜0.001）, and children with NOTCH1 mutations had a lower 4-year EFS rate than those of without mutations (71.5% vs 87.2%, P＝0.037).
Conclusion: Genetic mutations are prevalent in childhood ALL and mutations in tp53 and NOTCH1 are strong predictors of adverse outcomes in childhood ALL, with NGS contributing to the discovery of genetic mutations and timely adjustment of treatment regimens.
题目: 儿童急性淋巴细胞白血病患者基因突变谱与预后相关性的临床研究.
目的: 分析儿童急性淋巴细胞白血病（ALL）患者的基因突变谱，并探讨其对患儿预后的影响.
方法: 回顾性分析2018年1月至2021年12月于武汉儿童医院血液肿瘤科249例初诊ALL患儿的临床资料，采用靶向特异性二代测序（Next-generation sequencing, NGS）技术获得基因突变谱数据，并分析其与ALL患儿预后的相关性.
结果: 249例患儿中B-ALL 227例（91.2%），T-ALL 22例（8.8%）；178例（71.5%）患儿检测发现基因突变，其中85例（34.1%）患儿存在≥3种基因突变。突变率较高的基因依次为NRAS（23.7%）、KRAS（22.9%）、FLT3（11.2%）、PTPN11（8.8%）、CREBBP（7.2%）、NOTCH1（6.4%），其中KRAS、FLT3、PTPN11、CREBBP突变主要在B-ALL中检出，而NOTCH1、FBXW7突变主要在T-ALL中检出。与B-ALL比较，T-ALL患儿基因突变发生率更高（χ2=5.573，P＜0.05），且更容易发生基因共突变（P＜0.05）。伴tp53突变的患儿预计4年无事件生存（EFS）率（47.9% vs 88.5%，P＜0.001）以及OS率（53.8% vs 94.1%，P＜0.001）显著低于不伴有tp53突变的患儿，NOTCH1突变较无突变者初诊时更易发生高WBC增多血症（128.64×109/L vs 8.23×109/L，P＜0.001），伴NOTCH1突变的患儿4年EFS率低于无突变组（71.5% vs 87.2%，P=0.037）.
结论: 儿童ALL普遍存在基因突变，tp53和NOTCH1突变是儿童ALL不良结局的有力预测因子，NGS有助于发现基因突变而及时调整治疗方案.
Keywords: acute lymphoblastic leukemia; genetic variants; next-generation sequencing; prognosis.