Gene-expression profiles of Evi-1–high leukemias with MLL rearrangement revealed a stem cell–like character. (A) A strong correlation of up-regulated genes in EVI-1–high leukemias with a gene set representing HSCs and of down-regulated genes in EVI-1–high leukemias with a gene set typical of progenitor cells is shown. GSEA of gene expression in human EVI-1–high AMLs with MLL rearrangement (n = 5) was compared with EVI-1–low AMLs with MLL rearrangement (n = 8) using functional gene sets (C2). (Ai,ii) GSEA enrichment plots of the selected gene sets. (Ai) Up-regulated genes in human HSCs.⁴¹  (Aii) Up-regulated genes in hematopoietic late progenitor cells.³²  The corresponding heat maps represent expression of the 30 leading genes of the respective gene sets. Up-regulated and down-regulated genes are shown in red and blue, respectively. (B) GSEA plots show that expression of genes representing long-term HSCs (LTHSC) is enriched in EVI-1–high AMLs with MLL rearrangement compared with EVI-1–low AMLs with MLL rearrangement. Normalized enrichment score = 1.33; false-discovery rate q = .141. (C) GSEA of gene expression in 5 normal KSL samples and 4 normal GMP samples using a gene set representing EVI-1 high leukemia with MLL rearrangement. GSEA plots show that expression of genes representing EVI-1–high leukemia is enriched in KSL cells compared with GMPs. Normalized enrichment score = 1.46; false-discovery rate q = .025. (D) A strong correlation of up-regulated genes in EVI-1–high leukemias with those in cytoplasmic nucleophosmin–positive (NPMc⁺) leukemias existed. GSEA of gene expression in human EVI-1–high AMLs with MLL rearrangement (n = 5) was compared with EVI-1–low AMLs with MLL rearrangement (n = 8) using functional gene sets (C2). (Di-ii) GSEA enrichment plots of the selected gene sets. (Di) Up-regulated genes in NPMc⁺ leukemias.⁴²  (Dii) Down-regulated genes in NPMc⁺ leukemias.⁴²