Fig. 4: The iKMT2A-MLLT3 AML expression signature reflects the origin of TPO-exposed HSC.

A PCA shows a marked separation of the gene expression signatures of KME AML cells by TPO exposure of the donors with only a minor influence of Evi1 expression. B AML cells emerging from TPO-treated KME BM expressed similar or higher Evi1 and Erg levels than LT-HSC, or GMP-derived iKMT2A-MLLT3 blasts reported earlier⁹. C Venn diagram showing the number of common DEGs the different AML cell fractions (Evi1⁺, Evi1^-, and bulk) emerging from TPO- vs. PBS-stimulated KME BM cells. D Volcano plot of DEGs in Evi1⁺ AML cells emerging from TPO- or PBS-stimulated KME BM cells. E GSEA (MSigDB) analysis of DEGs in AML cells emerging from TPO- or PBS-treated KME BM cells revealed associations to signatures of aberrant Hoxa9 activity in both, the bulk and Evi1⁺ cell fractions. F KEGG analysis of DEGs in AML cells (bulk) emerging from TPO- or PBS-treated KME BM cells revealed up-regulation JAK-STAT and NF-κB signaling pathways. G GSEA revealed significant upregulation of JAK-STAT (top) and MAPK (bottom) pathways related genes in bulk blasts from symptomatic mice transplanted with TPO-treated KME BM cells. H GSEA revealed significant upregulation of the Biocarta (MSig-DB) TPO pathway-related genes in bulk blasts from symptomatic mice transplanted with TPO-treated KME BM cells. p-values were calculated with quasi-likelihood F-tests from EdgeR package (D) or permutation test of GSEA function from clusterProfiler R package (E–H).