Molecular and functional analysis of LSCs in patients with post-MPN AML. (A) Latent semantic index projection of 4020 cells from 9 patients with MPN and 8507 cells from 14 patients with post-MPN AML, and the expression of BCL2L1 onto the healthy donor (HD) hematopoietic hierarchy atlas shown in supplemental Figure 2E. (B) Latent semantic index projection of the same cell shown in panel A and the expression of BCL2 onto the HD hematopoietic hierarchy atlas shown in supplemental Figure 2E. (C) Three-dimensional diffusion map of 8000 Lin−CD34+ cells from 13 patients with post-MPN AML colored by genotype (left). (D-E) Three-dimensional diffusion map of the same cells from panel C colored by score of megakaryocyte development (D) and erythroid progenitor (E). (F-G) Three-dimensional diffusion map of the same cell shown in panel C colored by BCL2L1 expression (F) and BCL2 expression (G). (H) The expression of BCL2L1 in the leukemic MEPs (Jak2V617F/+Trp53–/– and Jak2V617F/+Trp53R172H/–) compared with MEP derived from mice at the chronic MPN stage. ∗∗∗∗P < .0001; ∗∗∗P < .001. DC, diffusion component; UMAP, uniform manifold approximation and projection.