Direct MECOM gene network is repressed in primary leukemia cells. (A) UMAP of 40 866 cells derived from 11 patients with leukemias driven by MLLrs sequenced using scRNA-seq. UMAPs were colored from top to bottom by patient, whether MECOM is expressed, and MECOM expression counts per cell. (B) Same UMAPs as panel A and colored by the expression signatures of normal HSCs and normal monocytes derived from Lambo et al36 and MECOM-regulated genes identified to be activated after depletion of MECOM (Figure 2). (C) Quantification of the 3 signatures from panel B compared between MECOM-positive leukemias (n = 5) and MECOM-negative leukemias (n = 6). Comparisons were performed by randomly taking the average over 10 iterations of 1000 randomly sampled cells from both samples expressing MECOM and samples not expressing MECOM to avoid uninformative P values close to 0. Significance was calculated using 2-sided Wilcoxon signed-rank tests corrected for multiple testing using BH. (D) Differential expression of all analyzed genes (n = 28 113) between leukemias expressing MECOM and leukemias that did not express MECOM. Differential expression was performed using MAST using 10 iterations of 1000 randomly selected MECOM-positive cells and 1000 randomly selected MECOM-negative cells to prevent uninformative P values. BH corrected P values and log fold changes shown are the average of 10 iterations. BH, Benjamini-Hochberg; UMAP, uniform manifold approximation and projection.
