Department of Pediatrics, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China.
Department of Medical Affairs, Acornmed Biotechnology Co., Ltd., Tianjin 301799, China.
Comput Math Methods Med. 2022 Aug 16;2022:7904293. doi: 10.1155/2022/7904293. eCollection 2022.
This study investigated the types and significance of mutant genes in children with acute lymphoblastic leukemia (ALL).
The gene sequencing data of 89 ALL children were retrospectively analyzed. Log-rank test was used to analyze the effect of different numbers of mutant genes on the clinical characteristics of the patients and disease.
Known gene mutations were detected in 64% (57/89) of the children, including one gene mutation in 31% and two or more gene mutations in 33% of the patients. Gene sequencing showed that most mutations occurred in KRAS (17%), NRAS (15%), FLT3 (7%), TP53 (7%), and PTPN11 (7%), and functional clustering analysis showed that most were signaling pathway genes (50%). In the overall cohort, no association was found between clinical characteristics and gene mutation. The children were then classified into three groups: group A (no gene mutation), group B (one gene mutation), and group C (two or more gene mutations). Correlation analysis showed that group A had significantly more children with medium risk ALL ( = 0.037), and group C had markedly more children with high risk ALL ( = 0.001). Further analysis showed that children with mutant genes took significantly more time to enter the maintenance phase than children without mutations.
Children with ALL had a high gene mutation rate, especially in KRAS and NRAS genes, and the mutant genes were mainly signal pathway-related. The gene mutations were significantly correlated with clinical phenotype and the time taken to enter the maintenance phase.
本研究旨在探讨儿童急性淋巴细胞白血病（ALL）突变基因的类型及其意义。
回顾性分析 89 例 ALL 患儿的基因测序数据。采用对数秩检验分析不同突变基因数量对患儿临床特征和疾病的影响。
检测到 64%（57/89）的患儿存在已知基因突变，其中 31%的患儿存在 1 个基因突变，33%的患儿存在 2 个或以上基因突变。基因测序显示，大多数突变发生在 KRAS（17%）、NRAS（15%）、FLT3（7%）、TP53（7%）和 PTPN11（7%），功能聚类分析显示，大多数为信号通路基因（50%）。在全队列中，临床特征与基因突变之间无关联。将患儿分为三组：A 组（无基因突变）、B 组（1 个基因突变）和 C 组（2 个或以上基因突变）。相关性分析显示，A 组中中危 ALL 患儿明显更多（ = 0.037），C 组中高危 ALL 患儿明显更多（ = 0.001）。进一步分析显示，突变基因患儿进入维持阶段的时间明显长于无突变患儿。
ALL 患儿基因突变率较高，尤以 KRAS 和 NRAS 基因多见，突变基因主要与信号通路相关。基因突变与临床表型及进入维持阶段的时间显著相关。
