Fig. 6: The pre-leukemic KMT2A::AFF1 signature is transferable to leukemic patient samples. | Leukemia

Fig. 6: The pre-leukemic KMT2A::AFF1 signature is transferable to leukemic patient samples.

From: Ontogeny-specific induction of the KMT2A::AFF1-fusion drives development of a distinct CD24 positive pre-leukemic state

Fig. 6

A UMAPs of LSK, PreProBs and ProBs from control and KMT2A::AFF1Vav-Cre+ embryos, highlighting PreProBs in control (top) and KMT2A::AFF1Vav-cre+ (bottom), respectively. B UMAP of PreProBs from control and KMT2A::AFF1Vav-Cre+ embryos, with the different clusters (left) and displaying the cells from cluster #5 on the UMAP from Fig. 5B (right). C Venn diagram of up- and downregulated genes in cluster #5 compared to control PreProBs and control cells in cluster #0 from the combined UMAP (“molecular HSC cluster”). The universal up- and downregulated genes formed the pre-leukemic signature. D UMAP displaying co-expression of Hmga2 and Cd24a in KMT2A::AFF1 expressing cells at E18.5 (left) and in postnatally induced mice (right). Pie charts show percentage of cells expressing each gene in Cre+ and Cre- cells, respectively. E Boxplot showing z-scored mean expression of the up-regulated genes from the pre-leukemic signature in different subtypes of ALL (n = 67–254) from bulk RNA-seq samples [46]. The box includes first to third quartile and the line indicates the median. F UMAP of healthy BM [48]. G Expression of the pre-leukemic signature in individual KMT2A::AFF1 infant ALL samples [47], mapped onto the UMAP in panel (F). Color scale set to the same range for all samples (0.35). Ages of the patients are listed on top. H Lack of expression of the pre-leukemic signature in the healthy BM reference. I Bar plots displaying predicted cell type (from healthy BM in F) of the signature positive cells in KMT2A::AFF1 leukemic patient samples [47]. J Violin plot displaying the UCell score of the pre-leukemic signature among different KMT2A rearranged infant ALLs [48]. K Boxplot of HMGA2 expression in different subtypes of ALL (n = 67–254) [46] displayed per age group. The box includes first to third quartile and the line indicates the median. L Heatmap displaying expression of selected genes in CD24+CD19- cells from KMT2A::AFF1 infants [47]. ****p adj  ≤ 0.0001.

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