Development of ABT-199 resistance in the splenic niche of ETP-ALL xenograft models. (A) Experimental design for in vivo study. Fourteen female nonobese diabetic/severe combined immunodeficient ϒ (NSG) mice were injected with luciferase-positive LOUCY cells (LOUCY GFP⁺ LUC⁺) by intravenous tail vein injection. After leukemia establishment, the mice were randomized to either vehicle or ABT-199 (50 mg/kg) treatment daily for 14 days. (B) The bioluminescence²¹  was recorded after injection of luciferin on days 0, 3, 7, 10, and 14. Each column of pictures represents 1 individual mouse. (C) The total bioluminescence signals (mean ± SEM) were plotted relative to the starting value at day 0 for each mouse. (D) Peripheral blood hCD45⁺ cells count measured weekly by flow cytometry. Mean ± SEM for each group were plotted. (E) The total bioluminescence imaging (BLI) signals (mean ± SEM) from the spleen and the hind legs during 14 days of treatment were measured and plotted as relative to the starting value at day 0 for each mouse. (F) Percentages of hCD45⁺ in blood, bone marrow, and spleen in mice given vehicle (n = 7) or ABT-199 (n = 7 for blood; n = 4 for bone marrow and spleen) at the end point treatment. (G) Spleen weight for mice treated with vehicle (n = 7) and ABT-199 (n = 4) were measured (right panel). Median values are indicated by horizontal bars (mean ± SEM). Two-way analysis of variance test was used to calculate P values. Statistically significant differences are indicated: **P ≤ .01, ***P ≤ .001, ****P ≤ .0001.