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Series GSE67046 Query DataSets for GSE67046
Status Public on Mar 24, 2015
Title NALP3 inflammasome up-regulation and CASP1 cleavage of the glucocorticoid receptor causes glucocorticoid resistance in leukemia cells [ChIP-Seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Glucocorticoids are universally used in the treatment of acute lymphoblastic leukemia (ALL), and glucocorticoid resistance in leukemia cells confers a poor prognosis. To elucidate mechanisms of glucocorticoid resistance, we determined the prednisolone sensitivity of primary leukemia cells from 444 newly diagnosed ALL patients and found significantly higher expression of caspase 1 (CASP1) and its activator NLRP3 in glucocorticoid resistant leukemia cells, due to significantly lower somatic methylation of CASP1 and NLRP3 promoters. Over-expression of CASP1 resulted in cleavage of the glucocorticoid receptor, diminished glucocorticoid-induced transcriptional response and increased glucocorticoid resistance. Knockdown or inhibition of CASP1 significantly increased glucocorticoid receptor levels and mitigated glucocorticoid resistance in CASP1 overexpressing ALL. Our findings establish a new mechanism by which the NLRP3/CASP1 inflammasome modulates cellular levels of the glucocorticoid receptor and diminishes cell sensitivity to glucocorticoids. The broad impact on glucocorticoid transcriptional response suggests this mechanism could also modify glucocorticoid effects in other diseases.
 
Overall design Duplicate treatments of two conditions (wild type and CASP1) including input controls
 
Contributor(s) Paugh SW, Yang W, Evans WE
Citation(s) 25938942, 32885175
Submission date Mar 18, 2015
Last update date Sep 08, 2020
Contact name Steven William Paugh
E-mail(s) steven.paugh@stjude.org
Phone 901-595-8680
Organization name St. Jude Children's Research Hospital
Department Pharmaceutical Sciences Department
Lab William E. Evans
Street address 262 Danny Thomas Place
City Memphis
State/province TN
ZIP/Postal code 38105
Country USA
 
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (6)
GSM1637305 Wild type input control
GSM1637306 Wild type Replicate 1
GSM1637307 Wild type Replicate 2
This SubSeries is part of SuperSeries:
GSE66708 NALP3 inflammasome up-regulation and CASP1 cleavage of the glucocorticoid receptor causes glucocorticoid resistance in leukemia cells
Relations
BioProject PRJNA278777
SRA SRP056299

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE67046_RAW.tar 300.0 Kb (http)(custom) TAR (of BED)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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