Paugh Steven W, Bonten Erik J, Evans William E
Hematological Malignancies Program, and Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital , Memphis, TN, USA.
Mol Cell Oncol. 2015 Nov 11;3(1):e1065947. doi: 10.1080/23723556.2015.1065947. eCollection 2016 Jan.
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.
在对糖皮质激素表现出原发性耐药的急性淋巴细胞白血病细胞中,我们最近发现半胱天冬酶1(CASP1)和含pyrin结构域的NLR家族成员3(NLRP3)的启动子甲基化减少,这导致转录增加、组成型NALP3(含NACHT、LRR和PYD结构域的蛋白3)炎性小体激活以及半胱天冬酶1介导的糖皮质激素受体裂解。这揭示了一种在模型系统中得以重现的糖皮质激素耐药新机制。