In primary acute lymphoblastic leukemia cells exhibiting de novo resistance to glucocorticoids, we recently discovered decreased promoter methylation of caspase 1 (CASP1) and NLR family, pyrin domain containing 3 (NLRP3), which resulted in increased transcription, constitutive NALP3 (NACHT, LRR and PYD domains-containing protein 3) inflammasome activation, and caspase 1-mediated cleavage of the glucocorticoid receptor. This revealed a novel mechanism of glucocorticoid resistance that was recapitulated in model systems.
Keywords: CASP1; NALP3; NR3C1; glucocorticoids; inflammasome.