Figure 7. Proposed mechanism of IL-4-induced apoptosis in AML.

Upon stimulation by IL-4, leukemic cells and neighboring cells produce increased CyPGs via COX-1/H-PGDS/PGD₂ axis as autocrine and paracrine secretions. CyPGs activate apoptotic signaling pathway (P53 and Caspase-3) by targeting PPARγ and/or P53 which leads to the remission of AML. IL-4 receptor-mediated signaling activates STAT6, which coordinates with PPARγ to up-regulate the expression of H-PGDS. Thus, PPARγ acts as a receptor for CyPGs to enhance endogenous production of CyPGs to partake in the anti-leukemic effects.