P300 inhibition blocks progression of AML. (A) Dose dependent effect of A-485 inhibitor on LSCs and WT LK cells proliferation. Cells were exposed to the indicated concentrations of A-485 for 48 h (n = 3; mean ± SD). (B) Surface expression of c-Kit in LSCs with A-485 (500 nM) treatment for 48 hours. (C) Cell-cycle profile in LSCs with A-485 (500 nM) treatment for 48 hours. (n = 3; mean ± SD). (D) Schematic representation of the treatment protocol. Four mice groups (5 or 6 mice per group) were treated with either vehicle or A-485 from days 3 to 22 (early-arm) and days 28 to 47 (late-arm) with 100 mg/kg once daily after LSCs transplantation. (E) Kaplan-Meier plot of A-485- and vehicle-treated mice (n = 5 or 6). P value was generated using Mantel-Cox log-rank test. (F) Leukemia burden (number of c-Kit⁺ cells) in the bone marrow and spleen of vehicle- and A-485–treated mice euthanized at matched time points. Data are representative of 3 biological replicates and error bars represent SD of the mean. (G) Histological analysis of H&E-stained sections of the bone marrow, spleen, and liver from a representative vehicle-treated mouse and an age-matched A-485–treated mouse. Scale bar, 100 μm.∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001. H&E, hematoxylin and eosin; LK, Lin^-c-Kit⁺; WT, wild-type.