ArticleBlood advances2023
Enhancer remodeling drives MLL oncogene-dependent transcriptional dysregulation in leukemia stem cells.
Article in Blood advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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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
11 citing papers in PubMed, 17 citations in OpenAlex.
- Epigenetic regulation of cancer stemness.Signal transduction and targeted therapy · 2025Review
- Polyamines at the crossroad between cell metabolism and epigenetic regulation in acute leukemias.Cell death discovery · 2025Review
- Targeting EP300 in diffuse large b-cell lymphoma: efficacy of A485 and synergistic effects with XPO1 inhibition.BMC cancer · 2025Article
- The important role of the histone acetyltransferases p300/CBP in cancer and the promising anticancer effects of p300/CBP inhibitors.Cell biology and toxicology · 2025Review
- Super enhancers as key drivers of gene regulatory networks in normal and malignant hematopoiesis.Frontiers in cell and developmental biology · 2025Review
- Chromatin accessibility: biological functions, molecular mechanisms and therapeutic application.Signal transduction and targeted therapy · 2024Review
- Acetylation of Histone H3 in Cancer Progression and Prognosis.International journal of molecular sciences · 2024Review
- Recent Developments and Evolving Therapeutic Strategies in KMT2A-Rearranged Acute Leukemia.Cancer medicine · 2024Review
- The epigenetic regulators EP300/CREBBP represent promising therapeutic targets in MLL-rearranged acute myeloid leukemia.Cell death discovery · 2024Article
- A guide to epigenetics in leukaemia stem cells.Molecular oncology · 2023Review
- Molecular targets of spermidine: implications for cancer suppression.Cell stress · 2023Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 3 countries.
Funding
Abstract
Acute myeloid leukemia (AML) with mixed-lineage leukemia (MLL) gene rearrangement (MLLr) comprises a cellular hierarchy in which a subpopulation of cells serves as functional leukemia stem cells (LSCs). They are maintained by a unique gene expression program and chromatin states, which are thought to reflect the actions of enhancers. Here, we delineate the active enhancer landscape and observe pervasive enhancer malfunction in LSCs. Reconstruction of regulatory networks revealed a master set of hematopoietic transcription factors. We show that EP300 is an essential transcriptional coregulator for maintaining LSC oncogenic potential because it controls essential gene expression through modulation of H3K27 acetylation and assessments of transcription factor dependencies. Moreover, the EP300 inhibitor A-485 affects LSC growth by targeting enhancer activity via histone acetyltransferase domain inhibition. Together, these data implicate a perturbed MLLr-specific enhancer accessibility landscape, suggesting the possibility for disruption of the LSC enhancer regulatory axis as a promising therapeutic strategy in AML.
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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.