Identification of a circular RNA isoform of WASHC2A as a prognostic factor for high-risk paediatric B-ALL patients.

Pediatric B-cell acute lymphoblastic leukemia (B-ALL) is a serious disease for which a better understanding of prognostic factors and new therapeutic targets is needed. Circular RNAs (circRNAs) are promising markers due to their stability and differential expression patterns in various diseases. However, their role in pediatric B-ALL patients, particularly in risk stratification and relapse prediction, remains poorly understood. In this study, we comprehensively examined the circRNA landscape in pediatric B-ALL patients, focusing on both high-risk and standard-risk patients. Using advanced sequencing techniques and sophisticated bioinformatics tools, we identified thousands of circRNAs, including a novel circRNA derived from the WASHC2A gene, termed circWASHC2A. CircWASHC2A showed differential expression between high-risk and standard-risk patients and exhibited potential for predicting relapse in high-risk patients. Functional experiments highlighted a role for circWASHC2A in regulating cell cycle progression and mitochondrial respiratory activity in leukaemic cells. Transcriptomic analysis further supported these findings, suggesting the involvement of circWASHC2A in signalling pathways relevant to leukaemia pathogenesis. This study provides in-depth insights into the circRNA landscape of pediatric B-ALL patients and identifies circWASHC2A as a potential biomarker for risk stratification and relapse prediction, with significant implications for tailoring diagnostic and therapeutic strategies in this patient population.