Combination of Notch inhibitors and multiple targeted therapies leads to decreased tumor burden and prolonged survival in human T-ALL cell line xenograft model. (A) Schematic representation of human T-ALL cell line xenograft model and drug treatment study. (B) Representative bioluminescence imaging at days indicated after treatment of each group. (C) Quantification of tumor burden measured by bioluminescent signals at days indicated after treatment of each group, testing Notch inhibitors alone or in combination with PD-0332991. Y-axis shows log₁₀FC of signals on day 11 or day 18 after treatment comparing with initiation of treatment. Data are shown in box and whisker plots showing all data points. One-way ANOVA was performed. (D) Kaplan-Meier survival analysis of NSG mice within each treatment group testing Notch inhibitors, PD-0332991, or in combination. (E) Kaplan-Meier survival analysis of NSG mice within each treatment group, testing CB-103, MK-2206, or in combination. (F) Kaplan-Meier survival analysis of NSG mice within each treatment group, testing CB-103, venetoclax, or in combination. Experiments shown here were performed with the T-ALL cell line RPMI-8402. Log-rank (Mantel-Cox) test; P value as indicated, ∗P < .0332; ∗∗P < .0021; ∗∗∗P < .0002; ∗∗∗∗P < .0001.