Research Paper Volume 6, Issue 12 pp 1033—1048

Figure 8. Landscapes of clonal expansions in the simulated pools under different parameters of mutation DFE when cell fitness is modified by microenvironment.

(A) Shaded regions represent the plausible range of mutation DFE variance and rate increase over lifetime (for derivation see Fig. 4) under different proportions of mutations in the positive tail of the ENV DFE (B) Plots of shape match landscapes within the studied ranges of mutation DFE variance (σ; Y-axis) and mutation rate increase (X-axis). Colored landscapes represent age-dependent rates of somatic evolution as shown in the panel C. The proportion of ENV DFE variance in the positive tail is indicated in white text. Plausible ranges of mutation parameters from panel A are compared to mutation parameters that replicate exponentially increasing rates of somatic evolution that shape-match leukemia incidence curve. (C) Color scale for panel B; colors represent the goodness of shape match between age-dependent leukemia incidence (green line) and simulated clonal expansions (blue line depicts the share of the most successful clone at any given time). (D) Age-dependent average cell fitness decline in the simulated pool for the indicated values of mutation DFE (σ).