Inflammasome-mediated glucocorticoid resistance: The receptor rheostat.
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.
Hematological Malignancies Program, and Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital , Memphis, TN, USA.
Steven W
SW
Paugh
Hematological Malignancies Program, and Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital , Memphis, TN, USA.
Erik J
EJ
Bonten
Hematological Malignancies Program, and Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital , Memphis, TN, USA.
William E
WE
Evans
CASP1; NALP3; NR3C1; glucocorticoids; inflammasome