Genomic Determinants of Induction Failure and Persistent Prognostic Risk of FLT3-ITD in Pediatric Acute Myeloid Leukemia

Abstract

Simple Summary Induction failure (IF), the persistence of leukemia after initial chemotherapy, is associated with poor survival in children with acute myeloid leukemia (AML), yet its genetic basis remains incompletely understood. This study compared the genetic profiles of children with and without IF using two independent patient cohorts. We found that mutations in the FLT3 gene were consistently more common in children who failed induction, and that the NUP98-NSD1 fusion was strongly enriched in this group. Importantly, the high-risk marker FLT3-ITD remained associated with worse survival even in children who successfully achieved remission, showing that reaching remission does not eliminate this risk. These findings highlight the genetic heterogeneity of IF and support combining genetic information with treatment response to guide more individualized risk assessment and treatment decisions.