Based on our findings that 1) exposure of BCP-ALL cells to either forskolin, cAMP analogues, PGE2, or MSC cocultures inhibits p53 accumulation and cell death in a similar fashion [9-11], 2) MSCs secrete PGE2, 3) ALL cells are known to express functional EP2 receptors eliciting a cAMP response [24], and 4) the effect of MSC cocultures on BCP-ALL p53 levels and cell survival is inhibited by COX or PKA inhibitors, we suggest a model in which BCP-ALL cells are protected from DNA damage-induced p53 accumulation and cell death by BM stromal cells in a PGE2-cAMP-PKA-dependent manner (Figure 6). Here, TP53 is linked to acute lymphoblastic leukemia.