Fig. 5.

Impact of the self-renewal rate on the depth of the hierarchy. The figure is based on 600 simulated patients. a Examples for hierarchies of different depths. Colors are used to visualize clones of different depths. b Self-renewal rate of significant clones increases significantly (p<0.05 in t-test) with the depth of the clones in hierarchies. Considered are only patients with clonal hierarchies of depth 3. c Properties of the first clone in the hierarchy decides about the depth of the hierarchy. Only if self-renewal rate of the first clone is small enough deep hierarchies emerge. If self-renewal rate of the first clone is high, disease progression and death occur before deep hierarchies can establish. d Comparison of self-renewal rates of significant and insignificant clones of depth 2. Self-renewal rates of insignificant clones is significantly smaller than self-renewal rates of significant clones. This demonstrates that clones do not become significant if their self-renewal rate is too small. Some of the insignificant clones show high self-renewal rates. These clones have originated late during the disease and could not grow to a significant size before death of the patients. If proliferation rate is very slow, clones with high self-renewal cannot grow to a significant size. Proliferation rate has no impact on the depth of the hierarchy. Parameters: mutation rate ν=5·10⁻⁹, self-renewal and proliferation rates of the new clones are normally distributed with the mean of the distributions equal to proliferation and self-renewal rates of the parent clone and standard deviation equal to 0.005