Fig. 4: Assessment of clonal diversity in postchemotherapy HSPCs.

a, The Simpson’s evenness index of post-treatment HSPCs from our cohort compared to indices from internal normal control and normal individuals as reported in ref. ². b, Comparison of the Simpson’s evenness index between post-treatment HSPCs (n = 12) versus age-matched normal HSPCs (n = 6, samples from ref. ² and internal normal control combined). An unpaired two-sided t test was performed to assess statistical significance between normal donors and treated HSPCs. Data are presented as mean ± 95% CIs, *P < 0.05. c, Comparison of Simpson’s evenness index between HSPCs treated with cytotoxic chemotherapy (n = 7), noncytotoxic chemotherapy (n = 5) and age-matched normal control (n = 4). P value is obtained from unpaired one-sided t tests. Data are presented as mean ± 95% CIs. Asterisk indicates FDR < 0.05. d, The simulation illustrates the projected Shannon diversity index over time for a population of 100,000 HSPCs, modeled with the Moran model. Each violin plot at each timepoint represents the results of 100 independent simulations of the model. The black line represents scenarios where acquired mutations do not affect fitness; the red line includes some mutations conferring a selective advantage; the blue line indicates the introduction of chemotherapy at approximately ages 35–40 years. e, The simulation displays the Shannon diversity index over time, based on a random sampling of 100 HSPCs from a pool of 100,000, considering the emergence of chemotherapy-resistant mutations (for example, TP53 and PPM1D). FDR, false discovery rate.