Liquid biopsy in pediatric acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy, and despite advances in therapy, relapse remains a major cause of treatment failure. Liquid biopsy has emerged as a powerful, minimally invasive tool for real-time disease monitoring and prognostication in hematologic malignancies. This review summarizes recent progress in the application of liquid biopsy technologies in pediatric ALL, focusing on circulating tumor DNA (ctDNA), circulating microRNAs (miRNAs), and extracellular vesicles (EVs). We discuss their respective biological origins, detection platforms, and clinical utilities in diagnosis, risk stratification, and measurable residual disease (MRD) assessment. Particular attention is paid to pediatric-specific challenges such as limited blood volume, pre-analytical variability, and the need for sensitive assays adapted to the pediatric context. Furthermore, we highlight cutting-edge innovations in EV isolation, machine learning-based biomarker integration, and prospective clinical applications. Notably, bone marrow evaluation remains the irreplaceable gold standard for pediatric ALL diagnosis and MRD monitoring. Although most liquid biopsy approaches are still in early translational stages for pediatric ALL, accumulating evidence supports their complementary value for optimizing individualized patient management. Continued validation in large, prospective pediatric cohorts is essential to bring these technologies closer to clinical implementation.