A) Schematic of fetal liver retroviral transduction and in vivo treatment strategy (top). Daily body weight change for mice treated with either vehicle or 100 mg/kg EZM2302 for three weeks. n=9
B) Kaplan-Meier survival analysis of MLL-AF9 fetal liver recipient mice treated with EZM2302 or vehicle for 21 days. Treatment start and end are indicated. n= 9, long-rank p value is 0.005.
C) Dose response for the cellular viability of 16 AML cells lines and CD34+ cells treated in vitro with EPZ025654 for 10 days. IC50 values were calculated using a non-linear regression analysis.
D) Representative GSEA plots depicting the top upregulation of the p53 pathway (NES = 1.71, FDR = 0.015) and down-regulation of E2F targets (NES = −1.73, FDR = 0.002) in SKNO-1 cells treated with EPZ025654 for 7 days. Results are compared to SKNO-1 cells treated with DMSO.
E) Summary of L1000 analysis showing significant gene ontology biological processes enriched in 16 AML cell lines and CD34+ cells treated with 5 µM of EPZ025654 for 6 days. Results represent three biological replicates, and three technical replicates. Bar graphs represent the mean IC50 of three idependent experiments.
See also Tables S4 and S5.