Primary human T-ALL cells are killed by dasatinib and temsirolimus combination treatment. (A-B) Quantification of combination therapy responses in ex vivo treated patient-derived xenograft cells isolated directly from the spleen of leukemic mice. Dose-response curves following 72 hours of therapy treatment (A). Quantification of phosphorylated LCK+/S6K+ T-ALL cells for PDX 42512 and PDX TA10 following 30 minutes of drug treatment or 24 hours for PDX 44179 and PDX 24836 (B). Error bars denote ± standard deviation in panel A and SEM in panel B, n = 3 replicates per data point and green lines denote synergistic combination treatments. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001 by 2-tailed Student t test. Not significant (ns). (C-D) Primary patient samples following ex vivo combination treatment for 48 hours (ALLT-323, ALLT-373, and ALLT-5221) or 72 hours (ALLT-379, ALLT-6787, and ALLT-7891). Dose-response curves with green lines denote synergistic drug responses (C, average across duplicate samples shown). Synergy plots showing responses of drugs over varied dosing (D). Synergy scores were assigned using the Loewe method and significance of >10 denoting marked synergy (ALLT-323, ALLT-379, ALLT-373, and ALLT-6787).