ArticleNature genetics2015
NALP3 inflammasome upregulation and CASP1 cleavage of the glucocorticoid receptor cause glucocorticoid resistance in leukemia cells.
Registry-linked trialOpen access · greenAbstract read
In one paragraph
Article in Nature genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00137111 (Total XV - Total Therapy Study XV for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia), which is not on this map. Cited by 107 papers.
0numbers the graph read from it
0cells of the map it votes in
107citing papers in PubMed
15.6field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Total XV - Total Therapy Study XV for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia
Who cites it
107 citing papers in PubMed, 158 citations in OpenAlex.
- PACSIN2 rs2413739 influence on thiopurine pharmacokinetics: validation studies in pediatric patients.The pharmacogenomics journal · 2020Trial
- The role of NLRP3 inflammasome in 5-fluorouracil resistance of oral squamous cell carcinoma.Journal of experimental & clinical cancer research : CR · 2017Trial
- Caspase-6 Controls Lipid and Energy Metabolism in Diet-Induced Obesity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Epigenetic mechanisms and steroid-resistant nephrotic syndrome: The future potential for SRNS diagnosis.iScience · 2026Review
- The role of pharmacogenetics in the therapy regimen of acute lymphoblastic leukemia in children: recent discoveries and future perspectives.Pharmacological reports : PR · 2026Review
- Epigenetic regulation of PANoptosis: DNA methylation, histone modifications and non-coding RNAs.EXCLI journal · 2026Review
- Relapse in childhood B-cell precursor acute lymphoblastic leukemia: insights from transcriptomic signatures of diagnostic bone marrow.Frontiers in oncology · 2026Review
- miRNA dysregulation in depression: unraveling the interplay between neuroplasticity, HPA axis dysfunction, and neuroinflammation.Metabolic brain disease · 2025Review
- Pharmacogenomics Applied to Acute Leukemias: Identifying Clinically Relevant Genetic Variants.Biomedicines · 2025Review
- Therapeutic potential of canagliflozin in DEN/TAA-induced renal cancer: mechanistic insights into NLRP3/IL-6/STAT3 and AMPK signaling and oxidative stress regulation.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2025Article
- Integrative multi-omic analysis of NLRP3 inflammasome dysregulation and subtyping for personalized treatment in acute myeloid leukemia.Discover oncology · 2025Article
- Feeder Cell Detachment in Drug Response Profiling of Leukemia Cell Coculture Can Be Prevented by Conditioned Medium.Cancer medicine · 2025Article
- Role of stem-like cells in chemotherapy resistance and relapse in pediatric T-cell acute lymphoblastic leukemia.Nature communications · 2025Article
- Article
- Unraveling the Complex Interplay Between Neuroinflammation and Depression: A Comprehensive Review.International journal of molecular sciences · 2025Review
- IL-8 promotes pyroptosis through ERK pathway and mediates glucocorticoid resistance in chronic rhinosinusitis with nasal polyps.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Therapeutic Significance of NLRP3 Inflammasome in Cancer: Friend or Foe?International journal of molecular sciences · 2024Review
- Defining the Differential Corticosteroid Response Basis from Multiple Omics Approaches.International journal of molecular sciences · 2024Review
- Cell death: Revisiting the roads to ruin.Developmental cell · 2024Review
- Association between Inflammatory and Metabolic Biomarkers and Common Mental Disorders among Adults: 2015 Health Survey of São Paulo, SP, Brazil.Metabolites · 2024Article
47 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
45 authors at 5 institutions in 4 countries.
Steven W Paugh1] Hematological Malignancies Program, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. [2] Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.ORCID 0000000156979228
Erik J Bonten1] Hematological Malignancies Program, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. [2] Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Daniel SavicHudsonAlpha Institute for Biotechnology, Huntsville, Alabama, USA.
Laura B Ramsey1] Hematological Malignancies Program, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. [2] Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
William E Thierfelder1] Hematological Malignancies Program, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. [2] Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Prajwal GurungDepartment of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
R K Subbarao MalireddiDepartment of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Marcelo ActisDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Anand MayasundariDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Jaeki MinDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
David R CossHigh-Performance Computing Facility, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Lucas T Laudermilk1] Hematological Malignancies Program, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. [2] Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
John C PanettaDepartment of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
J Robert McCorkle1] Hematological Malignancies Program, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. [2] Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Yiping FanDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Kristine R Crews1] Hematological Malignancies Program, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. [2] Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Gabriele Stocco1] Hematological Malignancies Program, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. [2] Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.ORCID 0000000309645879
Mark R Wilkinson1] Hematological Malignancies Program, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. [2] Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Antonio M FerreiraHigh-Performance Computing Facility, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Cheng ChengDepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Wenjian Yang1] Hematological Malignancies Program, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. [2] Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Seth E Karol1] Hematological Malignancies Program, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. [2] Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. [3] Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Christian A Fernandez1] Hematological Malignancies Program, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. [2] Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Barthelemy Diouf1] Hematological Malignancies Program, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. [2] Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.ORCID 0000000239470611
Colton Smith1] Hematological Malignancies Program, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. [2] Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
J Kevin Hicks1] Hematological Malignancies Program, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. [2] Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Alessandra Zanut1] Hematological Malignancies Program, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. [2] Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Audrey Giordanengo1] Hematological Malignancies Program, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. [2] Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Daniel Crona1] Hematological Malignancies Program, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. [2] Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Joy J Bianchi1] Hematological Malignancies Program, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. [2] Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Linda Holmfeldt1] Hematological Malignancies Program, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. [2] Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.ORCID 0000000341403423
Charles G Mullighan1] Hematological Malignancies Program, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. [2] Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.ORCID 0000000218711850
Monique L den BoerDivision of Pediatric Oncology-Hematology, Erasmus University Medical Center, Sophia Children's Hospital, Rotterdam, the Netherlands.
Rob Pieters1] Division of Pediatric Oncology-Hematology, Erasmus University Medical Center, Sophia Children's Hospital, Rotterdam, the Netherlands. [2] Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Sima Jeha1] Hematological Malignancies Program, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. [2] Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Thomas L DunwellCentre for Rare Diseases and Personalized Medicine, University of Birmingham, Birmingham, UK.
Farida LatifCentre for Rare Diseases and Personalized Medicine, University of Birmingham, Birmingham, UK.
Deepa Bhojwani1] Hematological Malignancies Program, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. [2] Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
William L CarrollNew York University Cancer Institute, New York University Langone Medical Center, New York, New York, USA.
Ching-Hon Pui1] Hematological Malignancies Program, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. [2] Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Richard M MyersHudsonAlpha Institute for Biotechnology, Huntsville, Alabama, USA.
R Kiplin GuyDepartment of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Thirumala-Devi KannegantiDepartment of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Mary V Relling1] Hematological Malignancies Program, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. [2] Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
William E Evans1] Hematological Malignancies Program, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. [2] Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
St. Jude Children's Research Hospital · USErasmus MC · NLHudsonAlpha Institute for Biotechnology · USUniversity of Birmingham · GBNYU Langone Health · US
Funding
Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 1985 to 2026
$166.9MPHARMACOGENOMICS OF CHILDHOOD LEUKEMIA (ALL)R37CA036401 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI EVANS, WILLIAM E · 1987 to 2014
$9.7MPAARK4Kids-Pharmacogenomics of Anticancer Agents Research in ChildrenU01GM092666 · NIGMS · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI RELLING, MARY V · 2010 to 2014
$8.9MPROFESSIONAL ONCOLOGY EDUCATION PROGRAMR25CA023944 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI SUZANNE A. GRONEMEYER · 1986 to 2026
$8.3MNLR signaling in colitis and colorectal tumorigenesisR01CA163507 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI KANNEGANTI, THIRUMALA-DEVI · 2012 to 2020
$3.5MMicroRNA pharmacogenomics: implications for childhood leukemia (ALL)F32CA141762 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI PAUGH, STEVEN WILLIAM · 2009 to 2011
$157kNCI NIH HHS 3R37CA036401-26S1NCI NIH HHS CA21765NCI NIH HHS F32 CA141762NCI NIH HHS F32CA141762NCI NIH HHS P30 CA021765NCI NIH HHS R01 CA163507NCI NIH HHS R25 CA023944NCI NIH HHS R37 CA036401NCI NIH HHS R37CA36401NIGMS NIH HHS U01 GM092666NIGMS NIH HHS U01GM92666
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.
Indexed as
AdolescentAntineoplastic Agents, HormonalBase SequenceCarrier ProteinsCaspase 1ChildChild, PreschoolDNA MethylationDrug Resistance, NeoplasmDrug Screening Assays, AntitumorGene Expression Regulation, LeukemicHEK293 CellsHumansInfantInfant, NewbornInflammasomesAntineoplastic Agents, HormonalCarrier ProteinsCaspase 1InflammasomesNLR Family, Pyrin Domain-Containing 3 ProteinNLRP3 protein, humanPrednisoloneReceptors, Glucocorticoid
Identifiers
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Read underepoch 390
Registered trials
NCT00137111ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.