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X Demographics
Mendeley readers
Attention Score in Context
| Title |
NALP3 inflammasome upregulation and CASP1 cleavage of the glucocorticoid receptor cause glucocorticoid resistance in leukemia cells
|
|---|---|
| Published in |
Nature Genetics, May 2015
|
| DOI | 10.1038/ng.3283 |
| Pubmed ID | |
| Authors |
Steven W Paugh, Erik J Bonten, Daniel Savic, Laura B Ramsey, William E Thierfelder, Prajwal Gurung, R K Subbarao Malireddi, Marcelo Actis, Anand Mayasundari, Jaeki Min, David R Coss, Lucas T Laudermilk, John C Panetta, J Robert McCorkle, Yiping Fan, Kristine R Crews, Gabriele Stocco, Mark R Wilkinson, Antonio M Ferreira, Cheng Cheng, Wenjian Yang, Seth E Karol, Christian A Fernandez, Barthelemy Diouf, Colton Smith, J Kevin Hicks, Alessandra Zanut, Audrey Giordanengo, Daniel Crona, Joy J Bianchi, Linda Holmfeldt, Charles G Mullighan, Monique L den Boer, Rob Pieters, Sima Jeha, Thomas L Dunwell, Farida Latif, Deepa Bhojwani, William L Carroll, Ching-Hon Pui, Richard M Myers, R Kiplin Guy, Thirumala-Devi Kanneganti, Mary V Relling, William E Evans |
| Abstract |
Glucocorticoids are universally used in the treatment of acute lymphoblastic leukemia (ALL), and resistance to glucocorticoids in leukemia cells confers poor prognosis. To elucidate mechanisms of glucocorticoid resistance, we determined the prednisolone sensitivity of primary leukemia cells from 444 patients newly diagnosed with ALL and found significantly higher expression of CASP1 (encoding caspase 1) and its activator NLRP3 in glucocorticoid-resistant leukemia cells, resulting from significantly lower somatic methylation of the CASP1 and NLRP3 promoters. Overexpression of CASP1 resulted in cleavage of the glucocorticoid receptor, diminished the 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 the glucocorticoid transcriptional response suggests that this mechanism could also modify glucocorticoid effects in other diseases. |
X Demographics
The data shown below were collected from the profiles of 7 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 5 | 71% |
| Unknown | 2 | 29% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 3 | 43% |
| Members of the public | 3 | 43% |
| Practitioners (doctors, other healthcare professionals) | 1 | 14% |
Mendeley readers
The data shown below were compiled from readership statistics for 188 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 3 | 2% |
| France | 1 | <1% |
| Turkey | 1 | <1% |
| Spain | 1 | <1% |
| Norway | 1 | <1% |
| Unknown | 181 | 96% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 38 | 20% |
| Researcher | 25 | 13% |
| Student > Master | 19 | 10% |
| Student > Bachelor | 14 | 7% |
| Student > Doctoral Student | 12 | 6% |
| Other | 38 | 20% |
| Unknown | 42 | 22% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 39 | 21% |
| Biochemistry, Genetics and Molecular Biology | 29 | 15% |
| Medicine and Dentistry | 28 | 15% |
| Immunology and Microbiology | 15 | 8% |
| Neuroscience | 6 | 3% |
| Other | 21 | 11% |
| Unknown | 50 | 27% |
Attention Score in Context
This research output has an Altmetric Attention Score of 40. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 April 2024.
All research outputs
#951,689
of 24,262,436 outputs
Outputs from Nature Genetics
#1,659
of 7,389 outputs
Outputs of similar age
#11,923
of 268,544 outputs
Outputs of similar age from Nature Genetics
#38
of 90 outputs
Altmetric has tracked 24,262,436 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 96th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 7,389 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 42.5. This one has done well, scoring higher than 77% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 268,544 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 95% of its contemporaries.
We're also able to compare this research output to 90 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 58% of its contemporaries.