Prostaglandin E₂ stimulates PTGER4 expression, increases intracellular cAMP, and sensitizes primary T-ALL patient samples to dexamethasone. (A) RNA seq data from PDX samples showing PTGER (1-4) expression (N = 23 patient samples). (B) qPCR analysis of PTGER (1-4) mRNA levels in normal thymus (N = 3) or in primary T-ALL samples expanded in PDX (N = 7-8). (C) Intracellular cAMP levels determined by ELISA in 1 × 10⁶ primary T-ALL cells (DX-18) treated with vehicle or PGE₂ (20 μM) for 30 minutes. (D) NR3C1 protein levels in patient samples (DX-18, REL-14) treated with vehicle, dexamethasone (1 µM), or PGE₂ (20 μM) for 24 hours. (E) Relative viability by cell titer glo of T-ALL patient samples treated with increasing concentrations of dexamethasone (0-10 μM) in the absence or presence of PGE₂ (20 μM) for 72 hours. (F) qPCR analysis of NR3C1 target genes in T-ALL patient sample (DX-96) treated with vehicle, dexamethasone (1 μM), PGE₂ (20 μM), or the combination. (G-H) qPCR analysis of NR3C1 and PTGER4 in primary T-ALL patient samples after treatment with vehicle, dexamethasone (1 μM), PGE₂ (20 μM), or the combination (dexamethasone + PGE₂) for 6 hours: (G) DX-96 and (H) REL-18. All qPCR values were normalized to vehicle-treated cells. The results are averages of at least 3 independent experiments, and error bars represent SEM. *P < .05, **P < .01, ***P < .001.