Neoplasia | Teams Led by Jianxiang Wang and Shaowei Qiu Reveal Prognostic Heterogeneity in FLT3-ITD–Mutated AML: Clonal Origin and 13q UPD as Key Drivers
Acute myeloid leukemia (AML) is a highly heterogeneous hematologic malignancy. Approximately 20–30% of AML patients harbor FLT3 internal tandem duplication (FLT3-ITD) mutations. FLT3-ITD is a major driver mutation in AML and typically arises as a late genetic event during leukemogenesis, often coexisting with mutations in NPM1, DNMT3A, WT1, and others. Although FLT3-ITD is generally associated with poor prognosis, substantial variability in clinical outcomes has been observed among FLT3-ITD–positive patients. Previous studies have largely focused on the molecular characteristics of FLT3-ITD itself, while the impact of its clonal origin on prognosis has been underexplored. Moreover, the key genetic evolutionary mechanisms driving resistance during progression from newly diagnosed disease to relapsed/refractory (R/R) AML remain incompletely understood.









