PPARγ activation is central in the protective effect of Se-S in CML mice. Se-S diet increases expression of H-Pgds, leading to increased production of the PPARγ ligands Δ¹²-PGJ₂ and 15d-PGJ₂. PPARγ activation feeds this cycle forward. GW9662 inhibits PPARγ-dependent decrease in Stat5a activation and downstream transcription factors (including Cited2 and Hif2α) implicated in the maintenance of the LSC population. Antagonism of PPARγ by GW9662 interrupts the positive feedback loop activated by selenium supplementation. Solid lines indicate a direct relationship; dashed lines, indirect.