Illustrative simulations showing age-specific incidence curves predicted from single mutation conferring an “exponential phenotype.” Each point on the graph is the predicted annual rate of new clinical presentations, marked on the vertical axes, at each age, marked on the horizontal axes. The model was run on 107 individuals using a mutation rate of 10−9 per cell division. Circles joined by interrupted lines are observed data. The lowest predicted line on each graph, marked by triangles, results from the malignant stem cells having expected division/differentiation–apoptosis ratios of 1 (ie, no selective advantage), with successively higher curves resulting from ratios of 0.95, 0.9, 0.8, and 0.6 (indicated by ■, ◆, —, and -, respectively). The left-hand triad of panels is based on hematopoiesis being maintained by 18 stem-cell differentiation events per year and the right hand triad, 36 such events. The expected stem-cell binary fission rates per year used in the simulations are indicated on each graph.
