Extended Data Fig. 6: Changes in hierarchy composition at AML relapse.

A) Hierarchy composition of 44 matched diagnosis and relapse pairs. Top row depicts hierarchy composition at diagnosis while the bottom row depicts hierarchy composition at relapse. Samples from the same patient are aligned vertically. B) Relative abundance of each leukemic cell population from scRNA-seq of 12 diagnostic AMLs (van Galen et al, 2019) compared with 8 relapsed AMLs (Abbas et al, 2021). Statistical significance was evaluated through two-sided Wilcoxon rank-sum tests. Box plots indicate the range of the central 50% of the data, with the central line marking the median. Whiskers extend from each box to 1.5*(interquartile range). C-F) Evolution of paired diagnosis and relapse AML samples depicted through shifts in cellular hierarchies, evolution of genetic subclones, and changes in cell-type composition. C) Patient 303642, in which significant genetic evolution is accompanied by a dramatic shift in cellular hierarchy from GMP to primitive. D) Patient 1019, in which replacement of an NRAS and IDH2 positive clone with an IDH1 positive clone is associated with a modest shift in cellular hierarchy. E) Patient 4, in which a loss of monocytic blasts is accompanied by a modest decrease in the the size of an NRAS bearing clone. F) Patient 150288, in which extensive linear genetic evolution is not associated with any appreciable change in cell type composition.