ArticleOncotarget2012
Small-molecule inhibition of BRD4 as a new potent approach to eliminate leukemic stem- and progenitor cells in acute myeloid leukemia AML.
Article in Oncotarget, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 154 citations in OpenAlex.
- Epigenetic alterations in Myeloid Malignancies.Advances in experimental medicine and biology · 2026Review
- Recommended Tool Compounds: Thienotriazolodiazepines-Derivatized Chemical Probes to Target BET Bromodomains.ACS pharmacology & translational science · 2025Review
- Long Non-Coding RNAs as "MYC Facilitators".Pathophysiology : the official journal of the International Society for Pathophysiology · 2023Review
- Inhibition of bromodomain-containing protein 4 enhances the migration of esophageal squamous cell carcinoma cells by inducing cell autophagy.World journal of gastrointestinal oncology · 2022Article
- BRD4 degradation blocks expression of MYC and multiple forms of stem cell resistance in PhAmerican journal of hematology · 2022Article
- EEF2K silencing inhibits tumour progression through repressing SPP1 and synergises with BET inhibitors in melanoma.Clinical and translational medicine · 2022Article
- The Novel Oral BET-CBP/p300 Dual Inhibitor NEO2734 Is Highly Effective in Eradicating Acute Myeloid Leukemia Blasts and Stem/Progenitor Cells.HemaSphere · 2021Article
- Mitochondrial metabolism as a target for acute myeloid leukemia treatment.Cancer & metabolism · 2021Review
- Novel Targeted Therapeutics in Acute Myeloid Leukemia: an Embarrassment of Riches.Current hematologic malignancy reports · 2021Review
- Bromodomain protein BRD4 is an epigenetic activator of B7-H6 expression in acute myeloid leukemia.Oncoimmunology · 2021Article
- The Biological Significance of Targeting Acetylation-Mediated Gene Regulation for Designing New Mechanistic Tools and Potential Therapeutics.Biomolecules · 2021Review
- Cell-based and antibody-mediated immunotherapies directed against leukemic stem cells in acute myeloid leukemia: Perspectives and open issues.Stem cells translational medicine · 2020Review
- Article
- Myelodysplastic Syndromes: How to Recognize Risk and Avoid Acute Myeloid Leukemia Transformation.Current oncology reports · 2020Review
- DNA Damage Induces Dynamic Associations of BRD4/P-TEFb With Chromatin and Modulates Gene Transcription in a BRD4-Dependent and -Independent Manner.Frontiers in molecular biosciences · 2020Article
- An epigenetic screening determines BET proteins as targets to suppress self-renewal and tumorigenicity in canine mammary cancer cells.Scientific reports · 2019Article
- Modeling hematopoietic disorders in zebrafish.Disease models & mechanisms · 2019Review
- Immunotherapy-Based Targeting and Elimination of Leukemic Stem Cells in AML and CML.International journal of molecular sciences · 2019Review
- FCY-302, a Novel Small Molecule, Induces Apoptosis in Leukemia and Myeloma Cells by Attenuating Key Antioxidant and Mitochondrial Enzymes.Oncology research · 2019Article
- Super-enhancers: critical roles and therapeutic targets in hematologic malignancies.Journal of hematology & oncology · 2019Review
22 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
Abstract
Acute myeloid leukemia (AML) is a life-threatening stem cell disease characterized by uncontrolled proliferation and accumulation of myeloblasts. Using an advanced RNAi screen-approach in an AML mouse model we have recently identified the epigenetic 'reader' BRD4 as a promising target in AML. In the current study, we asked whether inhibition of BRD4 by a small-molecule inhibitor, JQ1, leads to growth-inhibition and apoptosis in primary human AML stem- and progenitor cells. Primary cell samples were obtained from 37 patients with freshly diagnosed AML (n=23) or refractory AML (n=14). BRD4 was found to be expressed at the mRNA and protein level in unfractionated AML cells as well as in highly enriched CD34⁺/CD38⁻ and CD34⁺/CD38⁺ stem- and progenitor cells in all patients examined. In unfractionated leukemic cells, submicromolar concentrations of JQ1 induced major growth-inhibitory effects (IC₅₀ 0.05-0.5 µM) in most samples, including cells derived from relapsed or refractory patients. In addition, JQ1 was found to induce apoptosis in CD34+/CD38⁻ and CD34⁺/CD38⁺ stem- and progenitor cells in all donors examined as evidenced by combined surface/Annexin-V staining. Moreover, we were able to show that JQ1 synergizes with ARA-C in inducing growth inhibition in AML cells. Together, the BRD4-targeting drug JQ1 exerts major anti-leukemic effects in a broad range of human AML subtypes, including relapsed and refractory patients and all relevant stem- and progenitor cell compartments, including CD34⁺/CD38⁻ and CD34⁺/CD38⁺ AML cells. These results characterize BRD4-inhibition as a promising new therapeutic approach in AML which should be further investigated in clinical trials.
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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.