CK2 inhibition augments cytotoxicity of doxorubicin in PDX models of primary high-risk B-ALL. NRG mice were transplanted via tail vein with primary B-ALL cells (2 × 10E6 cells/mouse) from 3 patients. Mice were randomly divided into 4 groups. Once engraftment was established (determined as described in "Methods"), mice were treated with CX4945 (CX) only, doxorubicin (DOX) only, CX+DOX, or with vehicle-only control as described in "Methods." (A-C) Mice were euthanized and evaluated for the presence of leukemia in BM and spleen at day 24 following the initiation of treatment. BM and spleen cells were harvested and counted, and also stained for flow cytometry to detect human B-cell markers (CD10 and CD19), mouse CD45, and 7-AAD as a dead cell marker (described in "Methods"). The percentage of the living B-ALL leukemia cells (i, iii) and total leukemia cells (ii, iv) in BM and spleen were calculated and graphed. The effect of drug treatment was assessed by Student t test. (D-F) Patient-derived xenografts established with B-ALL from patient 1 (D), patient 2 (E), and patient 3 (F) were treated for 22 days with CK2 inhibitors, CX-4945 (CX), doxorubicin (DOX) only, CX+DOX, or vehicle control and followed for survival. Survival curves were generated using the Kaplan-Meier method and differences in survival were analyzed by χ² test. **P < .01, ***P < .001, ****P < .0001.