ArticleBlood2014
Downregulation of RUNX1/CBFβ by MLL fusion proteins enhances hematopoietic stem cell self-renewal.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed, 31 citations in OpenAlex.
- Targeting Menin in Acute Myeloid Leukemia: Therapeutic Advances and Future Directions.Cancers · 2024Review
- An Update of Epigenetic Drugs for the Treatment of Cancers and Brain Diseases: A Comprehensive Review.Genes · 2023Review
- Dissection of the MEF2D-IRF8 transcriptional circuit dependency in acute myeloid leukemia.iScience · 2022Article
- Insufficiency of FZR1 disturbs HSC quiescence by inhibiting ubiquitin-dependent degradation of RUNX1 in aplastic anemia.Leukemia · 2022Article
- Cross-platform transcriptomic profiling of the response to recombinant human erythropoietin.Scientific reports · 2021Article
- RUNX1 Upregulates CENPE to Promote Leukemic Cell Proliferation.Frontiers in molecular biosciences · 2021Article
- The functions and clinical significance of circRNAs in hematological malignancies.Journal of hematology & oncology · 2020Review
- MBNL1 regulates essential alternative RNA splicing patterns in MLL-rearranged leukemia.Nature communications · 2020Article
- Transcriptional activation of CBFβ by CDK11Cell communication and signaling : CCS · 2019Article
- Pathobiological Pseudohypoxia as a Putative Mechanism Underlying Myelodysplastic Syndromes.Cancer discovery · 2018Article
- Mesenchymal glioblastoma constitutes a major ceRNA signature in the TGF-β pathway.Theranostics · 2018Article
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- Article
- Review
- The RUNX1-PU.1 axis in the control of hematopoiesis.International journal of hematology · 2015Review
Corrections and comments
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Authors and funding
22 authors at 11 institutions in 5 countries.
Funding
Abstract
RUNX1/CBFβ (core binding factor [CBF]) is a heterodimeric transcription factor complex that is frequently involved in chromosomal translocations, point mutations, or deletions in acute leukemia. The mixed lineage leukemia (MLL) gene is also frequently involved in chromosomal translocations or partial tandem duplication in acute leukemia. The MLL protein interacts with RUNX1 and prevents RUNX1 from ubiquitin-mediated degradation. RUNX1/CBFβ recruits MLL to regulate downstream target genes. However, the functional consequence of MLL fusions on RUNX1/CBFβ activity has not been fully understood. In this report, we show that MLL fusion proteins and the N-terminal MLL portion of MLL fusions downregulate RUNX1 and CBFβ protein expression via the MLL CXXC domain and flanking regions. We confirmed this finding in Mll-Af9 knock-in mice and human M4/M5 acute myeloid leukemia (AML) cell lines, with or without MLL translocations, showing that MLL translocations cause a hypomorph phenotype of RUNX1/CBFβ. Overexpression of RUNX1 inhibits the development of AML in Mll-Af9 knock-in mice; conversely, further reducing Runx1/Cbfβ levels accelerates MLL-AF9-mediated AML in bone marrow transplantation assays. These data reveal a newly defined negative regulation of RUNX1/CBFβ by MLL fusion proteins and suggest that targeting RUNX1/CBFβ levels may be a potential therapy for MLLs.
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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.