Figure 6.
Pevonedistat diminishes CD34+ engraftment and disease propagation in humanized patient-derived xenograft mouse models. (A) Percentage of hCD45+ cells in the PB of NSGS mice engrafted with CD34+ cells from MF530675 and after treatment with pevonedistat (60 mg/kg), ruxolitinib (90 mg/kg), or combination; n = 8 in all groups. ****P < .0001 by 2-way ANOVA with Dunnett’s multiple comparisons test. (B) Percentage of hCD45+ cells in the BM of NSGS mice across multiple weeks of treatment. ****P < .0001 by 1-way ANOVA with Dunnett’s multiple comparisons test. (C) Percentage of myeloid cells from hCD45+ cells. **P < .01; ***P < .001; ****P < .0001 by 2-way ANOVA with Dunnett’s multiple comparisons test. (D) Percentage of erythroid cells from hCD45-cells in the BM. **P < .01 by 1-way ANOVA with Dunnett’s multiple comparisons test. (E) Normalized spleen weight at endpoint. *P < .05 by 1-way ANOVA with Dunnett’s multiple comparisons test. (F) Percentage of hCD45+cells in the PB of NSGS mice engrafted with CD34+ cells from a second patient MF700869 and after treatment with pevonedistat (60 mg/kg), ruxolitinib (90 mg/kg), or combination; n = 6 (vehicle and ruxolitinib) and 7 (pevonedistat and combination). **P < .01; ***P < .001; ****P < .0001 by 2-way ANOVA with Dunnett’s multiple comparisons test. (G) Percentage of hCD45+ cells in the BM of NSGS mice across multiple weeks of treatment. **P < .01 by 1-way ANOVA with Dunnett’s multiple comparisons test. (H) Normalized spleen weight at endpoint. **P < .01; ***P < .001 by 1-way ANOVA with Dunnett’s multiple comparisons test.

Pevonedistat diminishes CD34+ engraftment and disease propagation in humanized patient-derived xenograft mouse models. (A) Percentage of hCD45+ cells in the PB of NSGS mice engrafted with CD34+ cells from MF530675 and after treatment with pevonedistat (60 mg/kg), ruxolitinib (90 mg/kg), or combination; n = 8 in all groups. ****P < .0001 by 2-way ANOVA with Dunnett’s multiple comparisons test. (B) Percentage of hCD45+ cells in the BM of NSGS mice across multiple weeks of treatment. ****P < .0001 by 1-way ANOVA with Dunnett’s multiple comparisons test. (C) Percentage of myeloid cells from hCD45+ cells. **P < .01; ***P < .001; ****P < .0001 by 2-way ANOVA with Dunnett’s multiple comparisons test. (D) Percentage of erythroid cells from hCD45-cells in the BM. **P < .01 by 1-way ANOVA with Dunnett’s multiple comparisons test. (E) Normalized spleen weight at endpoint. *P < .05 by 1-way ANOVA with Dunnett’s multiple comparisons test. (F) Percentage of hCD45+cells in the PB of NSGS mice engrafted with CD34+ cells from a second patient MF700869 and after treatment with pevonedistat (60 mg/kg), ruxolitinib (90 mg/kg), or combination; n = 6 (vehicle and ruxolitinib) and 7 (pevonedistat and combination). **P < .01; ***P < .001; ****P < .0001 by 2-way ANOVA with Dunnett’s multiple comparisons test. (G) Percentage of hCD45+ cells in the BM of NSGS mice across multiple weeks of treatment. **P < .01 by 1-way ANOVA with Dunnett’s multiple comparisons test. (H) Normalized spleen weight at endpoint. **P < .01; ***P < .001 by 1-way ANOVA with Dunnett’s multiple comparisons test.

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