MPN fitness levels are associated with clinical features and outcome. (A) Schematic of the strategy used to purify and assess 11 hematopoietic populations isolated from PB: HSC, multipotent progenitor (MPP), common lymphoid progenitor (CLP), common myeloid progenitor (CMP), megakaryocyte-erythroid progenitor (MEP), granulocyte-macrophage progenitor (GMP), erythroid precursor (EP), monocyte (Mono), neutrophil (PMN), T lymphocyte (T), and B lymphocyte (B). ddPCR, droplet digital polymerase chain reaction; FACS, fluorescence-activated cell sorter. (B) Heatmap of unsupervised, hierarchical, principal component clustering of 11-population JAK2^V617F MAFs for 107 patients with MPN. Four major fitness clusters (F1, F2, F3, F4) are highlighted with relevant clinical information indicated under the dendrogram, including diagnosis (Dx), age, duration of MPN (Dur), high-molecular risk mutation status (HMR), and treatment (Rx). Clinical outcome events are shown under the heatmap. (C) Composite fitness patterns of F1, F2, F3, F4 patient groups are presented within a hematopoiesis hierarchy with mean MAF shown for each population as a blue wedge and ± standard deviation (Stdev) indicated in translucent blue shading. (D) Radar plots showing the difference in mean MAF between immature stem and progenitors (HSC+MPP) and each of 9 progenitors and differentiated cells. *P < .05; **P < .01; ***P < .001.