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. 2022 Dec 1;15(1):e15631. doi: 10.15252/emmm.202115631

Figure 2. IMPDH inhibitors suppress the growth of MLL‐fusion leukemia in vivo .

Figure 2

  1. Experimental scheme used in (B and C). C57BL/6J mice were transplanted with MLL‐AF9‐GFP cells and were treated with vehicle or MMF or FF‐10501‐01.
  2. Kaplan–Meier survival curves of MLL‐AF9 leukemia mice treated with vehicle or MMF (n = 12 per group). Frequencies of GFP+ leukemic cells in peripheral blood at day10 are also shown (mean ± SEM) on the right side (vehicle: n = 3, MMF: n = 4). Unpaired Student's t‐test (two‐tailed) were used for pairwise comparisons of significance.
  3. Kaplan–Meier survival curves with vehicle (n = 5), FF‐10501‐01 (n = 10). Frequencies of GFP+ leukemic cells in peripheral blood at day10 are also shown (mean ± SEM) on the right side (vehicle: n = 5, FF‐10501‐01: n = 5). Unpaired Student's t‐test (two‐tailed) were used for pairwise comparisons of significance.
  4. Experimental scheme used in (E‐G). C57BL/6J mice were transplanted with MLL‐AF9‐GFP cells and were treated with vehicle or FF‐10501‐01 on day 11 and 12. GFP+ MLL‐AF9 leukemia cells collected from mice were analyzed on day 13.
  5. Wright‐Giemsa staining of MLL‐AF9 cells (Scale bar: 20 μm).
  6. Representative FCM plots of frequencies of c‐Kit+ Gr‐1− and Mac‐1+ Gr‐1+ in leukemic cells and their quantification of independent mice (n = 10 per group). Unpaired Student's t‐test (two‐tailed) were used for pairwise comparisons of significance.
  7. Cell‐cycle status (left) and apoptosis (right) were assessed. Frequencies of S/G2/M phase cells and Annexin V+ cells in GFP+ MLL‐AF9 leukemia cells (n = 10 per group). Two‐tailed unpaired t‐tests were used for the comparison.
  8. Experimental scheme used in (I and J). MPA‐sensitive patient AML#1 (MLL‐AF10) cells were transplanted to NRGS mice and treated with vehicle, MMF or FF‐10501‐01 5 days per week for 3 weeks.
  9. Kaplan–Meier survival curves of PDX‐transplanted leukemia mice treated with vehicle (n = 6), MMF (n = 5), or FF‐10501‐01 (n = 5).
  10. Frequency of human CD45+ cells in bone marrow at day 22 in mice described in (I). Ordinary one‐way ANOVA was used for the comparison.
  11. Experimental scheme (left). MLL‐AF9‐GFP cells were transplanted into immunocompetent C57BL/6J mice and immunodeficient NSG mice. Dose schedule with vehicle or FF‐10501‐01 are the same as described in (A). Kaplan–Meier survival curves were also shown on the right (NSG‐vehicle: n = 8, NSG‐FF‐10501‐01: n = 8, C57BL/6J‐vehicle: n = 6, C57BL/6J‐FF‐10501‐01: n = 6).

Data information: All data are shown as mean ± SEM. Log‐rank test was used to compare the survival curves.