ArticleCell death discovery2024
The epigenetic regulators EP300/CREBBP represent promising therapeutic targets in MLL-rearranged acute myeloid leukemia.
Article in Cell death discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Inhibition of the EP300/Notch Signaling Pathway Regulates Proliferation and Apoptosis in Oral Squamous Cell Carcinoma.Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology · 2026Article
- Combined EP300 and CREBBP Expression Levels Regulate Human Trophoblast Differentiation.International journal of molecular sciences · 2026Article
- Genomic Characterization of Epigenetic Regulator Gene Alterations in Juvenile Myelomonocytic Leukemia Through Whole-Exome Sequencing.Epigenomes · 2026Article
- Synergistic Antitumor Activity of HAT Inhibitor A485 and XPO1 Inhibitor KPT8602 in Multiple Myeloma.Cancer medicine · 2026Article
- Decoding the enhancer-driven regulatory network for lactoferrin across mammalian species.Zoological research · 2026Article
- Discovery of a paralog-selective p300 protein degrader with potent anti-cancer activity in hematological malignancies.Nature communications · 2026Article
- Identification of novelTherapeutic advances in hematology · 2026Article
- The prognostic marker NRIP1 is associated with tumor progression and immune infiltration in acute myeloid leukemia.Acta biochimica et biophysica Sinica · 2025Article
- Gene regulatory complexes: their role and regulation across normal and malignant hematopoiesis.Experimental hematology · 2025Review
- Shared chromatin remodeling mutations drive concurrent rhabdomyosarcoma and leukemia in a pediatric patient.Discover oncology · 2025Article
- Substituted 1,4-naphthoquinones for potential anticancer therapeutics:Computational and structural biotechnology journal · 2025Article
- Recent Developments and Evolving Therapeutic Strategies in KMT2A-Rearranged Acute Leukemia.Cancer medicine · 2024Review
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Authors and funding
12 authors.
Funding
Abstract
Acute myeloid leukemia (AML) with mixed-lineage leukemia (MLL) gene rearrangements (MLL-r) is an aggressive subtype of blood cancer with dismal prognosis, underscoring the urgent need for novel therapeutic strategies. E1A-binding protein (EP300) and CREB-binding protein (CREBBP) function as essential transcriptional coactivators and acetyltransferases, governing leukemogenesis through diverse mechanisms. Targeting EP300/CREBBP holds great promise for treating leukemia with some certain cytogenetic abnormalities. Here, we demonstrated that EP300 and CREBBP are core epigenetic regulators in the pathogenesis of MLL-r AML through assaying the transposase-accessible chromatin with high-throughput sequencing (ATAC-seq). Knocking-out EP300/CREBBP and inhibitor (A-485) treatment depressed the MLL-r cells proliferation, while the MLL wild-type cells remained uninfluenced. We found that the CDK4/RB/E2F axis was downregulated specifically in MLL-r AML cell after A-485 treatment by RNA-seq, western blot and cut-tag analyses. EP300/CREBBP inhibitor selectively exerted potent anti-leukemia activity through blocking the MLL-r-BET complex binding to H3K27Ac modification on critical genes loci, distinct from global histone acetylation. Collectively, our study identified EP300/CREBBP as a critical epigenetic driver of MLL-r leukemia and validated their therapeutic potential through targeting inhibition, offering a promising avenue for improving clinical outcomes in this aggressive leukemia.
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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.