Fig. 5

ZSTK-474 restored nelarabine sensitivity in MOLT-4 and P12-ICHIKAWA cells co-cultured with of HS-5 stromal cells and down-modulated PI3K and Bcl2 signaling. a Flow cytometric analysis of Annexin V-FITC/PI staining in T-ALL cells growing alone or in co-culture system with HS-5 cells and treated with nelarabine (5 μM for P12-ICHIKAWA cells, 2 μM for MOLT-4 cells) in a Transwell^@ system. Three hundred seventy-five thousand T-ALL cells were seeded in the upper chamber of the Transwell^@ system. The histograms are representative of three separate experiments. CTRL untreated cells. b Graph bars indicating apoptotic cells in response to combined treatment in single culture versus co-culture with HS-5 cells. Asterisks indicate statistically significant differences with respect to untreated cells (***P < 0.001, *P < 0.05). c Flow cytometric analysis of Annexin V-FITC/PI of MOLT-4 cells growing in co-culture with HS-5 stromal cells and treated with nelarabine 2 μM for 48 h in a Transwell^@ system. The histograms are representative of three separate experiments. d Flow cytometric analysis of p-AKT (Ser473) and Bcl2 in MOLT-4 cells growing alone or in co-culture with HS-5 stromal cells. The histograms are representative of three separate experiments