Extended Data Fig. 10: Distinct responses of high and low output AML clones to chemotherapy treatment.

a, Abundance (proportion) of each dominant clone from the primary transplantation shown across the Baseline #2 and Disease #2 timepoints of the secondary transplantation. Clone abundance in the bone marrow (top) and spleen (bottom) are shown. Difference to mean indicates the difference between mean frequencies of each clone in the primary versus secondary transplants. b, Proportions of secondary transplant clones for Donor mouse #1 and recipient Ptprc^a and NSG mice. High output clones contribute >5% of the total disease burden whereas Mid output clones contribute 1-5%. Low output clones contribute below 1% of the total disease burden. Points represent individual clones and are coloured according to their primary transplant clone identity. Low output clones are not coloured. c, UMAP projections of the integrated scRNA-seq dataset shown in Fig. 4 showing c-Myc expression, and module enrichment scores for the Boroviak Diapause, LSC and Ramalho stemness gene signatures. q10 = 10^th quantile, q90 = 90^th quantile. d, UMAP projections of Baseline timepoint scRNA-seq data from MLL-AF9 + Kras^G12D cells prior to transplantation. Top row left to right: Louvain clusters, embedded locations of cells comprising low to High output clones (red), Mid/High to low output clones (blue) clones that are extinguished with chemotherapy treatment (green) and clones that survive chemotherapy (purple). Bottom row left to right: Slpi expression, Cebpε expression B2m expression, module enrichment scores for the Boroviak Diapause and Fridman Senescence signatures. q10 = 10^th quantile, q90 = 90^th quantile. e, Gene expression heat map showing the top differentially expressed genes in cells comprising Mid/High to Low output and Low to High output clones in the Vehicle sample and at each treatment timepoint. Normalized expression shown on scale. f, Selected enriched Biological Process gene ontologies for the set of genes up and downregulated in Low to High output clones vs Mid/High to Low output clones in the Vehicle sample and at each treatment timepoint. g, Selected enriched Biological Process gene ontologies for the set of genes up and downregulated in Mid/High to Low output clones vs Low to High output clones in the Vehicle sample and at each treatment timepoint.