Clonal architecture of FLT3-ITD and acquired 13q uniparental disomy define prognostic heterogeneity and therapeutic vulnerabilities in acute myeloid leukemia.

ABSTRACT: Acute myeloid leukemia (AML) is characterized by the sequential accumulation of genetic mutations in hematopoietic stem/progenitor cells (HSPCs). The FLT3-ITD mutation, occurring in 20-30 % of AML cases, typically emerges as a late event. Despite its established association with adverse prognosis, significant outcome heterogeneity persists in FLT3-ITD AML. The clonal origin of FLT3-ITD may serve as a critical determinant of phenotypic and prognostic variability, though the underlying mechanisms remain poorly understood. This study enrolled 149 FLT3-ITD AML patients. Genomic and transcriptomic profiling defined four prognostic origin subtypes (DNMT3A/NPM1-mutation, IDH/NPM1-mutation, transcription factor [TF]-related lesion and other genetic lesion origin). Within the high risk DNMT3A/NPM1-

SUBMITTER: Lai A 

PROVIDER: S-EPMC12808504 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature