ArticleNature cancer2020
Integrative genomic analyses reveal mechanisms of glucocorticoid resistance in acute lymphoblastic leukemia.
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Article in Nature cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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49citing papers in PubMed
5.2field-weighted citation impact, top 3% of its field
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Who cites it
49 citing papers in PubMed, 92 citations in OpenAlex.
- The machine-learning classifier ALLCatchR2 identifies 20 T-ALL subtypes across cohorts and age groups.HemaSphere · 2026Article
- Multi-Omics Applications in Adult Acute Lymphoblastic Leukemia: From Biological Mechanisms to Precision Therapies.International journal of molecular sciences · 2026Review
- IntegrateALL: An end-to-end RNA-seq analysis pipeline for multilevel data extraction and interpretable subtype classification in B-precursor ALL.HemaSphere · 2026Article
- Epigenetic mechanisms and steroid-resistant nephrotic syndrome: The future potential for SRNS diagnosis.iScience · 2026Review
- ANXA1 overexpression promotes B cell acute lymphoblastic leukemia progression and resistance by regulating fatty acid metabolism through PI3K/Akt signaling.Molecular and cellular biochemistry · 2026Article
- The role of pharmacogenetics in the therapy regimen of acute lymphoblastic leukemia in children: recent discoveries and future perspectives.Pharmacological reports : PR · 2026Review
- Dissecting cellular ecosystem with single-cell CRISPR screens.Blood science (Baltimore, Md.) · 2025Article
- Diagnostic and prognostic biomarkers associated with histotype in advanced epithelial ovarian cancer.Scientific reports · 2025Article
- Somatic mtDNA mutations at intermediate levels of heteroplasmy are a source of functional heterogeneity among primary leukemic cells.Science advances · 2025Article
- Histone-, Receptor-, and Integrin-Related Gene Products and ADAM28 as Relevant to B-Cell Acute Lymphoblastic Leukemia (B-ALL).Current issues in molecular biology · 2025Article
- Ex vivo drug responses and molecular profiles of 597 pediatric acute lymphoblastic leukemia patients.HemaSphere · 2025Article
- FTO regulates ELK3-mediated metabolic rewiring and represents a unique therapeutic target in T cell leukemia.Science advances · 2025Article
- Article
- Pleiotropic Effects of an eQTL in the CELSR2/PSRC1/SORT1 Cluster That Associates With LDL-C and Resting Metabolic Rate.The Journal of clinical endocrinology and metabolism · 2025Article
- Perinatal glucocorticoid sensitivity in the preterm newborn: molecular mechanisms, endogenous determinants, and clinical implications.Frontiers in endocrinology · 2025Review
- Enhancer-promoter hubs organize transcriptional networks promoting oncogenesis and drug resistance.Nature communications · 2024Article
- Bootstrap Evaluation of Association Matrices (BEAM) for Integrating Multiple Omics Profiles with Multiple Outcomes.bioRxiv : the preprint server for biology · 2024Article
- Central role of the mTORC1 pathway in glucocorticoid activity against B-ALL cells.Blood neoplasia · 2024Article
- Investigation of inherited noncoding genetic variation impacting the pharmacogenomics of childhood acute lymphoblastic leukemia treatment.Nature communications · 2024Article
- Article
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Authors and funding
41 authors at 5 institutions in 1 country.
Robert J AutryHematological Malignancies Program and Center for Precision Medicine in Leukemia, St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID 0000-0002-6965-2942
Steven W PaughHematological Malignancies Program and Center for Precision Medicine in Leukemia, St. Jude Children's Research Hospital, Memphis, TN, USA.
Robert CarterDepartment of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Lei ShiDepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA.
Jingjing LiuDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID 0000-0002-8184-8382
Daniel C FergusonHematological Malignancies Program and Center for Precision Medicine in Leukemia, St. Jude Children's Research Hospital, Memphis, TN, USA.
Calvin E LauHematological Malignancies Program and Center for Precision Medicine in Leukemia, St. Jude Children's Research Hospital, Memphis, TN, USA.
Erik J BontenHematological Malignancies Program and Center for Precision Medicine in Leukemia, St. Jude Children's Research Hospital, Memphis, TN, USA.
Wenjian YangHematological Malignancies Program and Center for Precision Medicine in Leukemia, St. Jude Children's Research Hospital, Memphis, TN, USA.
J Robert McCorkleHematological Malignancies Program and Center for Precision Medicine in Leukemia, St. Jude Children's Research Hospital, Memphis, TN, USA.
Jordan A BeardHematological Malignancies Program and Center for Precision Medicine in Leukemia, St. Jude Children's Research Hospital, Memphis, TN, USA.
John C PanettaDepartment of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA.
Jonathan D DiedrichHematological Malignancies Program and Center for Precision Medicine in Leukemia, St. Jude Children's Research Hospital, Memphis, TN, USA.
Kristine R CrewsHematological Malignancies Program and Center for Precision Medicine in Leukemia, St. Jude Children's Research Hospital, Memphis, TN, USA.
Deqing PeiDepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA.
Christopher J CokeHematological Malignancies Program and Center for Precision Medicine in Leukemia, St. Jude Children's Research Hospital, Memphis, TN, USA.
Sivaraman NatarajanDepartment of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Alireza KhatamianDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Seth E KarolHematological Malignancies Program and Center for Precision Medicine in Leukemia, St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID 0000-0001-8113-8180
Elixabet Lopez-LopezHematological Malignancies Program and Center for Precision Medicine in Leukemia, St. Jude Children's Research Hospital, Memphis, TN, USA.
Barthelemy DioufHematological Malignancies Program and Center for Precision Medicine in Leukemia, St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID 0000-0002-3947-0611
Colton SmithHematological Malignancies Program and Center for Precision Medicine in Leukemia, St. Jude Children's Research Hospital, Memphis, TN, USA.
Yoshihiro GochoHematological Malignancies Program and Center for Precision Medicine in Leukemia, St. Jude Children's Research Hospital, Memphis, TN, USA.
Kohei HagiwaraDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Kathryn G RobertsHematological Malignancies Program and Center for Precision Medicine in Leukemia, St. Jude Children's Research Hospital, Memphis, TN, USA.
Stanley PoundsDepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID 0000-0002-9167-2114
Steven M KornblauDepartment of Leukemia, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID 0000-0002-5990-9548
Wendy StockHematopoiesis and Hematological Malignancies Program, University of Chicago, Chicago, IL, USA.
Elisabeth M PaiettaDepartment of Medicine, Albert Einstein College of Medicine, Montefiore Medical Center, North Division, Bronx, NY, USA.
Mark R LitzowDivision of Hematology and Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
Hiroto InabaHematological Malignancies Program and Center for Precision Medicine in Leukemia, St. Jude Children's Research Hospital, Memphis, TN, USA.
Charles G MullighanHematological Malignancies Program and Center for Precision Medicine in Leukemia, St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID 0000-0002-1871-1850
Sima JehaHematological Malignancies Program and Center for Precision Medicine in Leukemia, St. Jude Children's Research Hospital, Memphis, TN, USA.
Ching-Hon PuiHematological Malignancies Program and Center for Precision Medicine in Leukemia, St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID 0000-0003-0303-5658
Cheng ChengDepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA.
Daniel SavicHematological Malignancies Program and Center for Precision Medicine in Leukemia, St. Jude Children's Research Hospital, Memphis, TN, USA.
Jiyang YuDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Charles GawadDepartment of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Mary V RellingHematological Malignancies Program and Center for Precision Medicine in Leukemia, St. Jude Children's Research Hospital, Memphis, TN, USA.
Jun J YangHematological Malignancies Program and Center for Precision Medicine in Leukemia, St. Jude Children's Research Hospital, Memphis, TN, USA.ORCID 0000-0002-0770-9659
William E EvansHematological Malignancies Program and Center for Precision Medicine in Leukemia, St. Jude Children's Research Hospital, Memphis, TN, USA. William.Evans@stjude.org.ORCID 0000-0002-9333-5322
St. Jude Children's Research Hospital · USAlbert Einstein College of Medicine · USMayo Clinic in Arizona · USThe University of Texas MD Anderson Cancer Center · USUniversity of Chicago · US
Funding
Project-006U10CA180820 · NCI · ECOG-ACRIN MEDICAL RESEARCH FOUNDATION · PI Peter J ODwyer · 2014 to 2026
$167.6MViral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI SUZANNE J. BAKER · 1985 to 2026
$166.9MCPML - Project 3: Genome-wide Studies of Adverse EffectsP50GM115279 · NIGMS · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI LOH, MIGNON LEE-CHEUN, RELLING, MARY V · 2015 to 2019
$15.1MPAARK4Kids-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
$8.3MPharmacogenomics of Childhood Leukemia ALLR01CA036401 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI EVANS, WILLIAM E · 1985 to 2019
$3.6MCreating a Catalog of Cancer Clonotype Drug Sensitivities with Single-CellGenome SequencingDP2CA239145 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI GAWAD, CHARLES · 2018 to 2018
$2.3MNCI NIH HHS DP2 CA239145NCI NIH HHS L40 CA162153NCI NIH HHS P30 CA021765NCI NIH HHS R01 CA036401NCI NIH HHS R25 CA023944NCI NIH HHS U10 CA180820NIGMS NIH HHS P50 GM115279NIGMS NIH HHS U01 GM092666
Abstract
Identification of genomic and epigenomic determinants of drug resistance provides important insights for improving cancer treatment. Using agnostic genome-wide interrogation of mRNA and miRNA expression, DNA methylation, SNPs, CNAs and SNVs/Indels in primary human acute lymphoblastic leukemia cells, we identified 463 genomic features associated with glucocorticoid resistance. Gene-level aggregation identified 118 overlapping genes, 15 of which were confirmed by genome-wide CRISPR screen. Collectively, this identified 30 of 38 (79%) known glucocorticoid-resistance genes/miRNAs and all 38 known resistance pathways, while revealing 14 genes not previously associated with glucocorticoid-resistance. Single cell RNAseq and network-based transcriptomic modelling corroborated the top previously undiscovered gene, CELSR2. Manipulation of CELSR2 recapitulated glucocorticoid resistance in human leukemia cell lines and revealed a synergistic drug combination (prednisolone and venetoclax) that mitigated resistance in mouse xenograft models. These findings illustrate the power of an integrative genomic strategy for elucidating genes and pathways conferring drug resistance in cancer cells.
Indexed as
MicroRNAsPrecursor Cell Lymphoblastic Leukemia-LymphomaAnimalsDrug Resistance, NeoplasmGenomicsGlucocorticoidsHumansMiceGlucocorticoidsMicroRNAs
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