Clinicomolecular features and clonal evolution of KMT2A-PTD AML: prognostic impact of concurrent FLT3-ITD under 2022 ELN risk stratification

Acute myeloid leukemia (AML) with KMT2A abnormalities comprises two major biologically distinct entities: KMT2A rearrangements ( KMT2A -r) and KMT2A partial tandem duplication ( KMT2A -PTD) [ 1 , 2 ]. While most KMT2A -r subtypes (except KMT2A :: MLLT3 ) are classified as adverse-risk AML according to the 2022 European LeukemiaNet (ELN) recommendations, the biological characteristics and prognostic significance of KMT2A -PTD remain unclear [ 3 ]. Previous studies have reported heterogeneous clinical outcomes in patients with KMT2A -PTD AML, likely reflecting considerable molecular heterogeneity driven by diverse co-mutation profiles [ 4 , 5 , 6 , 7 ]. Here, we integrated clinicogenomic, transcriptomic, and longitudinal clonal evolution analyses to comprehensively characterize KMT2A -PTD AML and compare its biological features with those of KMT2A -r AML. We further evaluated the prognostic impact of concurrent mutations, including FLT3 -ITD, to determine whether specific co-occurring mutations define clinically distinct subgroups.