In this retrospective case-control study involving 424 pediatric patients diagnosed with Pediatric Acute Lymphoblastic Leukemia (ALL), the investigation focused on analyzing the clinical characteristics and prognosis associated with the Cyclin-dependent kinase inhibitor 2A/2B (CDKN2A/2B) gene. Treatment and evaluation followed the South China Children's Leukemia Group-ALL-2016 protocol (SCCLG-ALL-2016). Among the cohort, 92 patients (21.7%) exhibited CDKN2A/2B gene deletions, with 11.1% homozygous and 10.6% heterozygous deletions. Notably, ALL patients that do have CDKN2A/2B gene deletions tended to present at an older age (P = 0.001), demonstrate hepatosplenomegaly on palpation (P < 0.001), and exhibit a higher incidence of Central nervous system leukemia (CNSL) (P = 0.037) and T-ALL (P = 0.007). A significant correlation was observed between ALL that does have CDKN2A/2B gene deletions and ETV6::RUNX1-positive (8.7% vs. 19.3%, P = 0.017) and IKZF1 gene deletions (20.7% vs. 8.4%, P = 0.001). Survival analysis of 392 patients revealed no significant differences in 5-year relapse, Overall survival (OS), or Event-free survival (EFS) between ALL that does/ does not have CDKN2A/2B gene deletions. Subgroup analysis highlighted poorer prognosis among hepatosplenomegaly patients in the CDKN2A/2B gene deletion group, with a 5-year EFS of 81.8%, 95%CI (0.695-0.963), P = 0.05. Hepatosplenomegaly emerged as the most significant prognostic factor for EFS [HR = 2.306, 95%CI (1.192-4.461), P = 0.013]. Cox regression analyses identified covariates influencing prognosis, ALL with the CDKN2A/2B gene showing no significant impact on outcomes. In conclusion, while ALL that does have CDKN2A/2B gene deletions is associated with certain clinical characteristics and genetic aberrations, they did not significantly impact OS or EFS. Furthermore, subgroup analysis revealed a potential prognostic role of ALL that does have CDKN2A/2B deletions presenting with hepatosplenomegaly on palpation, emphasizing the importance of comprehensive risk stratification in treatment decision-making for this subgroup.
Keywords: CDKN2A/2B gene deletion; Pediatric ALL; clinical characteristics; prognosis analysis.
What is the context? Pediatric acute leukemia, notably Acute Lymphoblastic Leukemia (ALL), is a prominent childhood cancer in developed countries.CDKN2A/2B genes, crucial for tumor suppression via the Rb and TP53 pathways and G1/S cell cycle checkpoint control, are frequently dysregulated, primarily through deletion, methylation, or mutation, in childhood ALL.Heterogeneity exists in the literature regarding the impact of CDKN2A/B gene deletions on pediatric ALL prognosis, with studies reporting variable outcomes.What is new? In this study, we found that patients with CDKN2A/2B gene deletions tended to present at an older age, demonstrate hepatosplenomegaly upon palpation, and exhibit a higher incidence of central nervous system leukemia (CNSL) and T-ALL.In this study, chemotherapy followed the South China Children's Leukemia Group-All-2016 protocol, where IKZF1 gene deletion is classified as high-risk, prompting intensified chemotherapy for affected patients. A significant correlation was observed between CDKN2A/2B gene deletions and ETV6::RUNX1 gene fusion and IKZF1 gene deletions. However, survival analysis of patients revealed no significant differences in 5-year relapse, Overall survival (OS), or Event-free survival (EFS) between CDKN2A/2B gene deletion and non-deletion groups.Subgroup analysis highlighted poorer prognosis among hepatosplenomegaly patients in the CDKN2A/2B gene deletion group.What is the impact? This study elucidates the role of CDKN2A/2B genes in childhood ALL, emphasizing the importance of comprehensive risk stratification in treatment decision-making for this subgroup.