ArticleLeukemia2017
Novel BET protein proteolysis-targeting chimera exerts superior lethal activity than bromodomain inhibitor (BETi) against post-myeloproliferative neoplasm secondary (s) AML cells.
Article in Leukemia, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.
What it found
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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.
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Who cites it
109 citing papers in PubMed, 181 citations in OpenAlex.
- Targeted degradation of protein in hematologic malignancies: mechanisms, therapeutic strategies, and clinical prospects.Cancer gene therapy · 2026Review
- BRD proteins in human retroviral infection: emerging evidence from HIV-1 and future perspectives for HTLV-1.Molecular biology reports · 2026Review
- MYC Addiction as a Targetable Vulnerability in Nelarabine-Resistant T-Cell Acute Lymphoblastic Leukemia.Cancer science · 2026Article
- BRD2 upregulation as a pan-cancer adaptive resistance mechanism to BET inhibition.Cellular & molecular biology letters · 2026Article
- Epigenetic modifications in cancer drug resistance: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- GLP-1RA in JBMMSCs promoted osteogenic differentiation via modulating CREB and BRD4 signaling mediated proliferation and stemness.Scientific reports · 2025Article
- BRD2 Upregulation as a Pan-Cancer Adaptive Resistance Mechanism to BET Inhibition.bioRxiv : the preprint server for biology · 2025Article
- Enhancer regulation in cancer: from epigenetics to mArchives of pharmacal research · 2025Review
- Efficacy of a novel BCL-xL degrader, DT2216, in preclinical models of JAK2-mutated post-MPN AML.Blood · 2025Article
- Advancing brain tumor therapy: unveiling the potential of PROTACs for targeted protein degradation.Cytotechnology · 2025Review
- Article
- PROTAC-mediated conditional degradation of the WRN helicase as a potential strategy for selective killing of cancer cells with microsatellite instability.Scientific reports · 2024Article
- PROteolysis-Targeting Chimeras (PROTACs) in leukemia: overview and future perspectives.MedComm · 2024Review
- CRISPR screening identifies BET and mTOR inhibitor synergy in cholangiocarcinoma through serine glycine one carbon.JCI insight · 2024Article
- Degraders in epigenetic therapy: PROTACs and beyond.Theranostics · 2024Review
- Bromodomain and extraterminal (BET) proteins: biological functions, diseases, and targeted therapy.Signal transduction and targeted therapy · 2023Review
- Development of a covalent cereblon-based PROTAC employing a fluorosulfate warhead.RSC chemical biology · 2023Article
- Development of Potent and Selective Coactivator-Associated Arginine Methyltransferase 1 (CARM1) Degraders.Journal of medicinal chemistry · 2023Article
- Beyond canonical PROTAC: biological targeted protein degradation (bioTPD).Biomaterials research · 2023Review
- Targeting of epigenetic co-dependencies enhances anti-AML efficacy of Menin inhibitor in AML with MLL1-r or mutant NPM1.Blood cancer journal · 2023Article
49 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
21 authors at 5 institutions in 1 country.
Funding
Abstract
The PROTAC (proteolysis-targeting chimera) ARV-825 recruits bromodomain and extraterminal (BET) proteins to the E3 ubiquitin ligase cereblon, leading to degradation of BET proteins, including BRD4. Although the BET-protein inhibitor (BETi) OTX015 caused accumulation of BRD4, treatment with equimolar concentrations of ARV-825 caused sustained and profound depletion (>90%) of BRD4 and induced significantly more apoptosis in cultured and patient-derived (PD) CD34+ post-MPN sAML cells, while relatively sparing the CD34+ normal hematopoietic progenitor cells. RNA-Seq, Reverse Phase Protein Array and mass cytometry 'CyTOF' analyses demonstrated that ARV-825 caused greater perturbations in messenger RNA (mRNA) and protein expressions than OTX015 in sAML cells. Specifically, compared with OTX015, ARV-825 treatment caused more robust and sustained depletion of c-Myc, CDK4/6, JAK2, p-STAT3/5, PIM1 and Bcl-xL, while increasing the levels of p21 and p27. Compared with OTX015, PROTAC ARV-771 treatment caused greater reduction in leukemia burden and further improved survival of NSG mice engrafted with luciferase-expressing HEL92.1.7 cells. Co-treatment with ARV-825 and JAK inhibitor ruxolitinib was synergistically lethal against established and PD CD34+ sAML cells. Notably, ARV-825 induced high levels of apoptosis in the in vitro generated ruxolitinib-persister or ruxolitinib-resistant sAML cells. These findings strongly support the in vivo testing of the BRD4-PROTAC based combinations against post-MPN sAML.
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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.