ArticleCell2018
CBFβ-SMMHC Inhibition Triggers Apoptosis by Disrupting MYC Chromatin Dynamics in Acute Myeloid Leukemia.
Article in Cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 50 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
50 citing papers in PubMed, 93 citations in OpenAlex.
- Disrupting the CBFβ-SMMHC-RUNX1 oncogenic protein-protein interaction in inv(16) AML: from fusion biology to targeted therapy.Discover oncology · 2026Review
- CBFβ-SMMHC-driven leukemogenesis requires enhanced RUNX1-DNA binding affinity in mice.The Journal of clinical investigation · 2025Article
- Activation of a nongenetic AHR-ELMSAN1 axis optimizes BET-targeting therapy and suppresses leukemia stem cells in preclinical models.Science translational medicine · 2025Article
- Transcription factors in the development and treatment of immune disorders.Transcription · 2025Review
- The co-receptor Neuropilin-1 enhances proliferation in inv(16) acute myeloid leukemia via VEGF signaling.Leukemia · 2025Article
- Super-enhancers in tumors: unraveling recent advances in their role in Oncogenesis and the emergence of targeted therapies.Journal of translational medicine · 2025Review
- Opening and changing: mammalian SWI/SNF complexes in organ development and carcinogenesis.Open biology · 2024Review
- Phase separation of PML/RARα and BRD4 coassembled microspeckles governs transcriptional dysregulation in acute promyelocytic leukemia.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Integrated genomic/epigenomic analysis stratifies subtypes of clear cell ovarian carcinoma, highlighting their cellular origin.Scientific reports · 2024Article
- RUNX1 C-terminal mutations impair blood cell differentiation by perturbing specific enhancer-promoter networks.Blood advances · 2024Article
- Apoptosis-related prognostic biomarkers and potential targets for acute kidney injury based on machine learning algorithm and in vivo experiments.Apoptosis : an international journal on programmed cell death · 2024Article
- The multi-CDK inhibitor dinaciclib reverses bromo- and extra-terminal domain (BET) inhibitor resistance in acute myeloid leukemia via inhibition of Wnt/β-catenin signaling.Experimental hematology & oncology · 2024Article
- N-MYC regulates cell survival via eIF4G1 in inv(16) acute myeloid leukemia.Science advances · 2024Article
- The ncBAF Complex Regulates Transcription in AML Through H3K27ac Sensing by BRD9.Cancer research communications · 2024Article
- BloodChIP Xtra: an expanded database of comparative genome-wide transcription factor binding and gene-expression profiles in healthy human stem/progenitor subsets and leukemic cells.Nucleic acids research · 2024Article
- Proteogenomic analysis reveals cytoplasmic sequestration of RUNX1 by the acute myeloid leukemia-initiating CBFB::MYH11 oncofusion protein.The Journal of clinical investigation · 2023Article
- Shift of N-MYC Oncogene Expression in AML Patients Carrying the FLT3-ITD Mutation.Pathophysiology : the official journal of the International Society for Pathophysiology · 2023Article
- Reducing the inherent auto-inhibitory interaction within the pegRNA enhances prime editing efficiency.Nucleic acids research · 2023Article
- Review
- SWI/SNF complexes in hematological malignancies: biological implications and therapeutic opportunities.Molecular cancer · 2023Review
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
The fusion oncoprotein CBFβ-SMMHC, expressed in leukemia cases with chromosome 16 inversion, drives leukemia development and maintenance by altering the activity of the transcription factor RUNX1. Here, we demonstrate that CBFβ-SMMHC maintains cell viability by neutralizing RUNX1-mediated repression of MYC expression. Upon pharmacologic inhibition of the CBFβ-SMMHC/RUNX1 interaction, RUNX1 shows increased binding at three MYC distal enhancers, where it represses MYC expression by mediating the replacement of the SWI/SNF complex component BRG1 with the polycomb-repressive complex component RING1B, leading to apoptosis. Combining the CBFβ-SMMHC inhibitor with the BET inhibitor JQ1 eliminates inv(16) leukemia in human cells and a mouse model. Enhancer-interaction analysis indicated that the three enhancers are physically connected with the MYC promoter, and genome-editing analysis demonstrated that they are functionally implicated in deregulation of MYC expression. This study reveals a mechanism whereby CBFβ-SMMHC drives leukemia maintenance and suggests that inhibitors targeting chromatin activity may prove effective in inv(16) leukemia therapy.
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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.