Genomic Landscape of Relapsed Pediatric B-Cell Acute Lymphoblastic Leukemia
DOI:
https://doi.org/10.5281/zenodo.22818794Keywords:
B-cell ALL, relapse, clonal evolution, NT5C2, IKZF1Abstract
Background: Relapse remains the leading cause of leukemia-related death in children with B-cell acute lymphoblastic leukemia (B-ALL), and matched diagnosis-relapse sequencing studies over the past fifteen years have reframed relapse as the outgrowth of a genetically distinct, therapy-selected clone rather than a resurgence of the original tumor.
Objective: To synthesize the published genomic literature on clonal evolution, relapse-driver mutations, and relapse risk stratification in pediatric B-ALL, focusing on chemoresistance genes such as NT5C2 and PRPS1, glucocorticoid pathway alterations in NR3C1 and CREBBP, and structural lesions such as IKZF1 deletion.
Methods: Narrative review of peer-reviewed genomic-profiling studies of pediatric B-ALL diagnosis-relapse cohorts, clonal tracking and xenograft studies, and genomic risk-stratification and targeted-therapy reports identified through literature search.
Findings: Relapse clones are frequently detectable as minor subclones at diagnosis; thiopurine resistance is recurrently driven by NT5C2 and PRPS1 mutations; glucocorticoid resistance is linked to CREBBP and NR3C1 disruption; and IKZF1 deletion, IKZF1plus, and Ph-like kinase signatures mark relapse risk that is increasingly actionable with targeted agents.
Conclusions: Relapse genomics has matured from descriptive clonal-evolution studies into candidate diagnosis-time risk scores and druggable-lesion strategies, but most of this evidence remains retrospective and now requires prospective validation.
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