Figure 4.
Suz12 inactivation causes activation of the PI3K/mTOR, VEGF/VEGFR and WNT signaling pathways. (A) Results of overrepresentation enrichment analysis of the KEGG canonical pathways in the set of upregulated genes in JAK3(M511I)+Suz12gRNA leukemias (J+S1 vs J), ranked according to lowest false discovery rate (FDR). The number of genes within a pathway is indicated in brackets. (B) Similar analysis as in A, but now with the canonical pathways. (C-E) Drug dose response curves showing viability of (leukemia) cells in response to 24 hours of treatment with increasing concentrations of PI3K/mTOR inhibitor dactolisib (C), VEGFR inhibitor sunitinib (D), and WNT inhibitor PKF118-310 (E). HSPC, wild-type hematopoietic stem and progenitor cells; Thy, wild-type thymocytes. For all drug dose response curves, percentage viability is defined as percentage surviving cells relative to DMSO concentration. GI50 values are shown.

Suz12 inactivation causes activation of the PI3K/mTOR, VEGF/VEGFR and WNT signaling pathways. (A) Results of overrepresentation enrichment analysis of the KEGG canonical pathways in the set of upregulated genes in JAK3(M511I)+Suz12gRNA leukemias (J+S1 vs J), ranked according to lowest false discovery rate (FDR). The number of genes within a pathway is indicated in brackets. (B) Similar analysis as in A, but now with the canonical pathways. (C-E) Drug dose response curves showing viability of (leukemia) cells in response to 24 hours of treatment with increasing concentrations of PI3K/mTOR inhibitor dactolisib (C), VEGFR inhibitor sunitinib (D), and WNT inhibitor PKF118-310 (E). HSPC, wild-type hematopoietic stem and progenitor cells; Thy, wild-type thymocytes. For all drug dose response curves, percentage viability is defined as percentage surviving cells relative to DMSO concentration. GI50 values are shown.

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