CBFB-MYH11 fusion transcript subtypes are associated with distinct transcriptional landscapes. (A) GSEA comparing E5-E33 CBFB-MYH11 AMLs with all others, using gene sets available through the Molecular Signature Database (hallmark, curated, and oncogenic signature gene sets). Three gene sets that define CBFB-MYH11 transcriptional signatures are significantly enriched in E5-E33 CBFB-MYH11 AMLs. Specifically, the Ross et al gene set is associated with a normalized enrichment score of 2.42 (P value <.0001) with the displayed heatmap of enriched genes. (B) UMAP analysis revealed that E5-E33 CBFB-MYH11 AMLs occupy a different cluster than most other CBFB-MYH11 AMLs. (C) GSEA comparing E5-E33 CBFB-MYH11 AMLs with all others and using a gene set derived by Mandoli et al based on CBFB-MYH11 chromatin immunoprecipitation sequencing (ChIP-seq) occupancy reveals significant enrichment (normalized enrichment score of 1.37, P value <.0001) in E5-E33 CBFB-MYH11 AMLs (100 most enriched genes shown). Violin plots of representative genes within the Mandoli et al gene set that are associated with hematopoietic stem cells or early hematopoiesis (Mann-Whitney U test).