Genomic and Clinical Analysis of Children with Acute Lymphoblastic Leukemia

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 (P = 0.037), and group C had markedly more children with high risk ALL (P = 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.