Figure 5 | Scientific Reports

Figure 5

From: Using patient-derived iPSCs to develop humanized mouse models for chronic myelomonocytic leukemia and therapeutic drug identification, including liposomal clodronate

Figure 5

Drug discovery using CMML-iPSCs. (a) An MEK inhibitor (PD0325901) reduced the colony-forming capacity of CMML iPSC-derived HPCs (n = 3, independent experiments,, Normal-iPSCs1 from a healthy donor, and CMML-iPSCs1 from a CMML patients, Experiments were performed in triplicate. Statistical analyses were performed with ANOVA and the Dunnett post-test for multiple comparisons. ***p < 0.001)). (b) RAS inhibitor (salirasib) reduced the colony-forming capacity of CMML iPSC-derived HPCs (n = 3, independent experiments, Normal-iPSCs1 from a healthy donor, and CMML-iPSCs1 from a CMML patients, Experiments were performed in triplicate. Statistical analyses were performed with ANOVA and the Dunnett post-test for multiple comparisons. **p < 0.01). (c) pERK was constitutively activated only in the colonies of CMML iPSC-derived HPCs. Furthermore, ERK phosphorylation was inhibited by MEK and RAS inhibitors in these colonies. (d) The expression level of pERK was significantly decreased in CMML-iPSC-derived hematopoietic colonies by MEK or Ras inhibitor (n = 3, independent experiments, *p < 0.05, Normal-iPSCs1 from a healthy donor, and CMML-iPSCs1 from a CMML patients, paired two-sided t-test). (e) Liposomal clodronate suppressed the growth of colonies from CMML iPSCs. Statistical analysis was performed (n = 3, independent experiments, Normal-iPSCs1 from a healthy donor, and CMML-iPSCs1 from a CMML patients, Experiments were performed in triplicate. Statistical analyses were performed with ANOVA and the Dunnett post-test for multiple comparisons. ***p < 0.001, **p < 0.01,). (f) Liposomal clodronate reduced re-plating colonies formed by CMML iPSC-derived HPCs (n = 3, independent experiments, Normal-iPSCs1 from a healthy donor, and CMML-iPSCs1 from a CMML patients, Experiments were performed in triplicate. Statistical analyses were performed with ANOVA and the Dunnett post-test for multiple comparisons. ***p < 0.001). (g) Colony formation by three other primary samples from CMML patients was reduced by liposomal clodronate. Horizontal lines represent the means ± s.d.

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