ArticleLeukemia2019
Drug targeting of NR4A nuclear receptors for treatment of acute myeloid leukemia.
Article in Leukemia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- NR4A Family Genes: A Review of Comprehensive Prognostic and Gene Expression Profile Analysis in Breast Cancer.Frontiers in oncology · 2022Pooled it
- PROTAC-mediated targeting of IKKβ and NR4A1 for AML therapy.Oncogene · 2026Article
- Targeting Lineage-Specific Functions of NR4A1 for Cancer Immunotherapy.International journal of molecular sciences · 2025Review
- Loss of glucose-stimulated β-cell Nr4a1 expression impairs insulin secretion and glucose homeostasis.American journal of physiology. Cell physiology · 2024Article
- Excess BAFF Alters NR4As Expression Levels and Breg Function of Human Precursor-like Marginal Zone B-Cells in the Context of HIV-1 Infection.International journal of molecular sciences · 2022Article
- Functional association of NR4A3 downregulation with impaired differentiation in myeloid leukemogenesis.Annals of hematology · 2022Article
- Marginal Zone B-Cell Populations and Their Regulatory Potential in the Context of HIV and Other Chronic Inflammatory Conditions.International journal of molecular sciences · 2022Review
- Article
- Comprehensive insights into the function and molecular and pharmacological regulation of neuron-derived orphan receptor 1, an orphan receptor.Frontiers in pharmacology · 2022Review
- The Impact of Aging on the Lung Alveolar Environment, Predetermining Susceptibility to Respiratory Infections.Frontiers in aging · 2022Review
- Role of NR4A family members in myeloid cells and leukemia.Current research in immunology · 2022Article
- NR4A1-3 nuclear receptor activity and immune cell dysregulation in rheumatic diseases.Frontiers in medicine · 2022Review
- Orphan nuclear receptor 4A1 (NR4A1) and novel ligands.Essays in biochemistry · 2021Article
- NR4A family members regulate T cell tolerance to preserve immune homeostasis and suppress autoimmunity.JCI insight · 2021Article
- The Paradoxical Roles of Orphan Nuclear Receptor 4A (NR4A) in Cancer.Molecular cancer research : MCR · 2021Review
- Targeting NR4A Nuclear Receptors to Control Stromal Cell Inflammation, Metabolism, Angiogenesis, and Tumorigenesis.Frontiers in cell and developmental biology · 2021Review
- Transcriptional Profiling of Monocytes Deficient in Nuclear Orphan ReceptorsFrontiers in immunology · 2021Article
- PIK3Cδ expression by fibroblasts promotes triple-negative breast cancer progression.The Journal of clinical investigation · 2020Article
- Targeting Oncogenic Super Enhancers in MYC-Dependent AML Using a Small Molecule Activator of NR4A Nuclear Receptors.Scientific reports · 2020Article
- Novel Non-Coding Transcript inFrontiers in oncology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
NR4As are AML tumor suppressors that are frequently silenced in human acute myeloid leukemia (AML). Despite their potential as novel targets for therapeutic intervention, mechanisms of NR4A silencing and strategies for their reactivation remain poorly defined. Here we show that NR4A silencing in AML occurs through blockade of transcriptional elongation rather than epigenetic promoter silencing. By intersection of NR4A-regulated gene signatures captured upon acute, exogenous expression of NR4As in human AML cells with in silico chemical genomics screening, we identify several FDA-approved drugs including dihydroergotamine (DHE) that reactivate NR4A expression and regulate NR4A-dependent gene signatures. We show that DHE induces NR4A expression via recruitment of the super elongation complex to enable elongation of NR4A promoter paused RNA polymerase II. Finally, DHE exhibits AML selective NR4A-dependent anti-leukemic activity in cytogenetically distinct human AML cells in vitro and delays AML progression in mice revealing its potential as a novel therapeutic agent in AML.
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Identifiers
What OpenQuestion holds
Registered trials
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.