Fig. 1

Integrative RNA sequencing (RNA-seq) analysis of acute myeloid leukemia (AML) tumors. (A) Uniform Manifold Approximation and Projection for Dimension Reduction (UMAP) plot based on the top 1,000 most variable genes from 105 AML tumor RNA-seq samples. The analysis reveals three major AML subtypes, including RUNX1::RUNX1T1, APL (acute promyelocytic leukemia), and CBFB::MYH11, which are clearly separable from the others, while the remaining subtypes are not distinctly distinguished by gene expression alone. (B) Heatmap showing subtype-level gene expression profiles (column-wise normalized log₂[CPM]) across 13 AML subtypes with at least three samples (see Supplementary Table 1 for differentially expressed genes across 13 AML subtypes) Consistent with (A), although only the same three subtypes are apparently separated, the cluster branches specific to four AML subtypes, comprising RUNX1::RUNX1T1 (n = 25), APL (n = 7), CBFB::MYH11 (n = 9), and KMT2Ar (n = 14) , are highlighted in different colors. (C–F) Top genes with higher expression in each of these four AML subtypes are shown. (G) Gene set enrichment analysis (GSEA) of 50 Hallmark pathways based on differentially expressed genes for each of four subtypes highlighted in (B) compared to all other subtypes as controls.