Expansion of Kras-mutant cells resumes after the cessation of the therapy. (A) Contribution of Kras^G12D-mutant HSC to hematopoiesis after the treatment with KRAS^G12D inhibitor followed by recovery. Kras^G12D or WT reporter animals 3 wk after tamoxifen administration were treated with MRTX1133 or vehicle daily for 7 days (red arrows), followed by 3 wk of recovery and endpoint analysis. (B and C) Accrual of Tom⁺ cells in the blood after the treatment (week 4, B) or recovery (week 7, C). Shown are fractions of Tom⁺ cells within the indicated blood cell types in MRTX1133- or vehicle-treated WT (gray, top panels) or Kras^G12D (red, bottom panels) reporter mice. Note the different scales for WT and Kras^G12D mice, reflecting the expansion of Tom⁺ cells in the latter. (D–F) Accrual of Kras-mutant cells in reporter mice after the recovery from MRTX1133 treatment. Shown are the fractions of Tom⁺ cells in the mature cells in the spleen (D), stem/progenitor cells in the BM (E), and developing T cells in the thymus (F). In panels B–F, symbols represent individual mice; bars represent the mean ± SD of the data pooled from two independent experiments. Statistical significance was estimated by the Mann–Whitney test. *P < 0.05, **P < 0.01, ***P < 0.001.