ArticleLeukemia2015
Hes1 suppresses acute myeloid leukemia development through FLT3 repression.
Article in Leukemia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- DNA methylation in monozygotic twins discordant for acute lymphoblastic leukemia: a case report and systematic review.Clinical epigenetics · 2025Pooled it
- Novel molecular mechanisms of FLT3 deregulation: from the acute myeloid leukemia experience to therapeutic insights in acute lymphoblastic leukemia.Molecular cancer · 2025Review
- Hes1 in malignant tumors: from molecular mechanism to therapeutic potential.Frontiers in immunology · 2025Review
- Expanded profiling of WD repeat domain 5 inhibitors reveals actionable strategies for the treatment of hematologic malignancies.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Notch activator cyclopiazonic acid induces apoptosis in HL-60 cells through calcineurin activation.The Journal of antibiotics · 2024Article
- Uncovering NOTCH1 as a Promising Target in the Treatment ofInternational journal of molecular sciences · 2023Article
- The fatty acid elongase Elovl6 is crucial for hematopoietic stem cell engraftment and leukemia propagation.Leukemia · 2023Article
- Roles of transducin-like enhancer of split (TLE) family proteins in tumorigenesis and immune regulation.Frontiers in cell and developmental biology · 2022Review
- Review
- Notch Signaling in the Bone Marrow Lymphopoietic Niche.Frontiers in immunology · 2021Review
- Combined inhibition of Notch and FLT3 produces synergistic cytotoxic effects in FLT3/ITDSignal transduction and targeted therapy · 2020Article
- Antiproliferative and Immunoregulatory Effects of Azelaic Acid Against Acute Myeloid LeukemiaFrontiers in pharmacology · 2019Article
- Signaling Pathways in Leukemic Stem Cells.Advances in experimental medicine and biology · 2019Review
- Changes of signal transductivity and robustness of gene regulatory network in the carcinogenesis of leukemic subtypes via microarray sample data.Oncotarget · 2018Article
- The versatile nature of miR-9/9Oncotarget · 2018Review
- Meis2 as a critical player in MN1-induced leukemia.Blood cancer journal · 2017Article
- MiRNA182 regulates percentage of myeloid and erythroid cells in chronic myeloid leukemia.Cell death & disease · 2017Article
- Selective Inhibitors of Histone Deacetylases 1 and 2 Synergize with Azacitidine in Acute Myeloid Leukemia.PloS one · 2017Article
- Signaling and molecular basis of bone marrow niche angiogenesis in leukemia.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2016Review
- MicroRNA-9 promotes proliferation of leukemia cells in adult CD34-positive acute myeloid leukemia with normal karyotype by downregulation of Hes1.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In leukemogenesis, Notch signaling can be up and downregulated in a context-dependent manner. The transcription factor hairy and enhancer of split-1 (Hes1) is well-characterized as a downstream target of Notch signaling. Hes1 encodes a basic helix-loop-helix-type protein, and represses target gene expression. Here, we report that deletion of the Hes1 gene in mice promotes acute myeloid leukemia (AML) development induced by the MLL-AF9 fusion protein. We then found that Hes1 directly bound to the promoter region of the FMS-like tyrosine kinase 3 (FLT3) gene and downregulated the promoter activity. FLT3 was consequently upregulated in MLL-AF9-expressing immortalized and leukemia cells with a Hes1- or RBPJ-null background. MLL-AF9-expressing Hes1-null AML cells showed enhanced proliferation and ERK phosphorylation following FLT3 ligand stimulation. FLT3 inhibition efficiently abrogated proliferation of MLL-AF9-induced Hes1-null AML cells. Furthermore, an agonistic anti-Notch2 antibody induced apoptosis of MLL-AF9-induced AML cells in a Hes1-wild type but not a Hes1-null background. We also accessed two independent databases containing messenger RNA (mRNA) expression profiles and found that the expression level of FLT3 mRNA was negatively correlated with those of HES1 in patient AML samples. These observations demonstrate that Hes1 mediates tumor suppressive roles of Notch signaling in AML development, probably by downregulating FLT3 expression.
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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.