ArticleCancer research2023
SWI/SNF Blockade Disrupts PU.1-Directed Enhancer Programs in Normal Hematopoietic Cells and Acute Myeloid Leukemia.
Article in Cancer research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 42 citations in OpenAlex.
- Review
- The roles of chromatin remodeling and 3D genome organization in cancers: from mechanistic insights to emerging treatment options.Molecular cancer · 2026Review
- Selective sensitivity of Ph-like B-cell acute lymphoblastic leukemia to BRG1 inhibition identifies a therapeutic vulnerability.Leukemia · 2026Article
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- A SWI/SNF-specific Ig-like domain, SWIFT, is a transcription factor binding platform.Science (New York, N.Y.) · 2026Article
- YY1 nitration participates in DbCM cardiomyocyte lipotoxicity by inhibiting ANXA3-induced microlipophagy.Redox biology · 2026Article
- Highly effective combination of BRG1/BRM inhibitor with BET inhibitor or decitabine for high-risk MECOM-rearranged AML.HemaSphere · 2026Article
- The lncRNA ELDR suppresses tumorigenicity of AML by interfering with DNA replication and chromatin accessibility.Blood advances · 2025Article
- Nascent CUT&Tag captures transcription factor binding after chromatin duplication.bioRxiv : the preprint server for biology · 2025Article
- β-catenin functions as a molecular adapter for disordered cBAF interactions.Molecular cell · 2025Article
- Eomesodermin in conjunction with the BAF complex promotes expansion and invasion of the trophectoderm lineage.Nature communications · 2025Article
- Chromatin remodeling in lymphocytic function and fate: the multifaceted roles of SWI/SNF complex.Frontiers in immunology · 2025Review
- Epigenetic mechanisms of drug resistance in acute myeloid leukemia: advances in small-molecule targeted therapy.Frontiers in pharmacology · 2025Review
- Pharmacologic Blockade of a Pioneer Transcription Factor.Cancer research · 2024Article
- Notch induces transcription by stimulating release of paused RNA polymerase II.Genes & development · 2024Article
- Opening and changing: mammalian SWI/SNF complexes in organ development and carcinogenesis.Open biology · 2024Review
- Electrochemical impedance spectroscopy unmasks high-risk atherosclerotic features in human coronary artery disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Chromatin remodellers as therapeutic targets.Nature reviews. Drug discovery · 2024Review
- Baf155 controls hematopoietic differentiation and regeneration through chromatin priming.Cell reports · 2024Article
- Targeting the mSWI/SNF complex in POU2F-POU2AF transcription factor-driven malignancies.Cancer cell · 2024Article
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 3 countries.
Funding
Abstract
In acute myeloid leukemia (AML), SWI/SNF chromatin remodeling complexes sustain leukemic identity by driving high levels of MYC. Previous studies have implicated the hematopoietic transcription factor PU.1 (SPI1) as an important target of SWI/SNF inhibition, but PU.1 is widely regarded to have pioneer-like activity. As a result, many questions have remained regarding the interplay between PU.1 and SWI/SNF in AML as well as normal hematopoiesis. Here we found that PU.1 binds to most of its targets in a SWI/SNF-independent manner and recruits SWI/SNF to promote accessibility for other AML core regulatory factors, including RUNX1, LMO2, and MEIS1. SWI/SNF inhibition in AML cells reduced DNA accessibility and binding of these factors at PU.1 sites and redistributed PU.1 to promoters. Analysis of nontumor hematopoietic cells revealed that similar effects also impair PU.1-dependent B-cell and monocyte populations. Nevertheless, SWI/SNF inhibition induced profound therapeutic response in an immunocompetent AML mouse model as well as in primary human AML samples. In vivo, SWI/SNF inhibition promoted leukemic differentiation and reduced the leukemic stem cell burden in bone marrow but also induced leukopenia. These results reveal a variable therapeutic window for SWI/SNF blockade in AML and highlight important off-tumor effects of such therapies in immunocompetent settings. SIGNIFICANCE: Disruption of PU.1-directed enhancer programs upon SWI/SNF inhibition causes differentiation of AML cells and induces leukopenia of PU.1-dependent B cells and monocytes, revealing the on- and off-tumor effects of SWI/SNF blockade.
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Registered trials
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