Genetic associations with progressive TKI resistance. (A) Cell type–specific clusters, in which >50% of cells are contributed by the CD34⁺ HSPCs of any 1 sample, were identified. Cell type clusters (eg, ERP-11, HSC-2, and LyP-1) are as described in supplemental Tables 9 and 10A,B. (B) CML samples with patient-specific clusters in panel A are shown in the UMAP space. Letters in parenthesis refer to the prognostic group (A, B, or C) each sample belongs to. (C) Genes that are frequently mutated in CML were compiled from the literature (supplemental Table 23), and their mutational status was assessed by WES. Oncoplot of somatic mutations in selected genes, colored by the type of mutation. The frequency of each mutation (%) is shown to the right of the plot. A total of 40 such variants were identified, as shown in supplemental Table 23. (D) To cross-reference the 40 SNVs identified in panel C, to our scRNA-seq data set, cb_sniffer was used (“Methods”). The asterisk indicates that the variant could be successfully detected within the scRNA reads of the same sample. (E) Cross-referencing variants identified in panel C to individual cell types. For any given variant, only the most recurrent cell type has been plotted. The complete data set is shown as supplemental Table 24B. Variants that can be detected in T/NK clusters have been highlighted with an orange rectangle. It should be noted that given the design of the 10× Genomics single cell technology, the absence of variant detection does not imply the absence of expression. Supplemental Figure 10 and supplemental Tables 22-24 are linked with the data in Figure 5.