cAMP pathway activation synergizes with dexamethasone to reverse GC resistance in human T-ALL cells. Relative cell viability by cell titer glo of KOPTK1 (A) or CUTLL1 (C) cells after treatment with dexamethasone (0-10 μM), forskolin (0-100 µM), and IBMX (100 μM) or the combination (dexamethasone/forsoklin/IBMX) for 72 hours. Data are normalized to vehicle-treated cells. Isobologram plot showing synergism between forskolin/IBMX and dexamethasone treatment in human T-ALL cell lines KOPTK1 (B) and CUTLL1 (D). (E) Human T-ALL cell lines were treated with vehicle, forskolin (10 μM), and IBMX (100 μM), dexamethasone (1 μM), or with the combination (dexamethasone, forskolin/IBMX) for 72 hours, and Annexin V/7AAD-positive cells were determined by flow cytometry. (F) Relative viability by cell titer glo of 4 T-ALL patient samples (GC sensitive: TALL-x-7 and 18; GC resistant: TALL-x-14 and 10) treated in vitro with vehicle or dexamethasone (1 μM) in the presence or absence of forskolin (10 μM) for 72 hours. Data are normalized to vehicle-treated cells. (G) Intracellular cAMP levels in 2 × 10⁶ primary TALL-x-18 cells treated with vehicle or forsoklin for 30 minutes. The results are averages of at least 3 independent experiments, and error bars represent SEM. *P < .05, **P < .01, ***P < .001.