This study aimed to explore the correlation between the deletion of the CDKN2A/B gene and the prognosis of pediatric acute lymphoblastic leukemia (ALL) patients. A total of 310 pediatric patients who were diagnosed with acute lymphoblastic leukemia at our hospital from January 2020 to September 2023 were included in this study. Among them, 78 patients with CDKN2A/B deletion were included in the final analysis. Additionally, 78 ALL patients without CDKN2A/B deletion, who were diagnosed during the same period, were randomly selected for comparison. A statistical analysis was conducted to compare the clinical characteristics and prognosis between the CDKN2A/B deletion group and the non-deletion group in ALL patients. The results showed that pediatric ALL patients with CDKN2A/B deletion had higher white blood cell counts and a greater proportion of immature cells in peripheral blood at diagnosis. The age at diagnosis was older in the deletion group, with a greater proportion in the >
10-year-old group. CDKN2A/B deletion occurred more frequently in pediatric patients with T-ALL than in pediatric patients with B-ALL. Patients with CDKN2A/B deletion were more likely to have positive BCR-ABL1 expression combined with IKZF1 deletion. The overall survival (OS) rate was 89.7%, and the event-free survival (EFS) rate was 83.3% in the CDKN2A/B deletion group, which was lower than the OS rate of 97.4% and EFS rate of 93.6% in the non-deletion group. These results suggest that CDKN2A/B deletion may be one of the factors affecting poor prognosis. It provides a new perspective for clinical treatment, risk stratification, and prognostic assessment in pediatric ALL patients.