ArticleCell death & disease2021
A KDM4A-PAF1-mediated epigenomic network is essential for acute myeloid leukemia cell self-renewal and survival.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 33 citations in OpenAlex.
- Dynamic regulation of H3K9 modifications in cancer: pathogenesis and targeted therapies.Biomarker research · 2026Review
- The nutrigenomic-epigenetic axis in cancer: from dietary bioactives to precision oncology.Nutrition & metabolism · 2026Review
- Selective small molecule targeting of KDM4 as a therapeutic strategy to reduce proliferation of acute myeloid leukaemia.British journal of haematology · 2026Article
- The JMJD family histone demethylases: structure, mechanism of action, diseases and therapeutic targets.Molecular biomedicine · 2026Review
- chromIDEAS reveals epigenetic dynamics via multi-dimensional clustering of chromatin states.Nucleic acids research · 2026Article
- Histone demethylase KDM4A promotes endometrial cancer progression through an ERRγ-associated cell-cycle regulatory axis.International journal of biological sciences · 2026Article
- KDM4A-induced tumor senescence enhances the efficacy of immunotherapy by inhibiting AGT-PHB1 axis-mediated mitophagy in colorectal cancer.Autophagy · 2025Article
- KDM4A-driven SMAD5/TGFβ axis activation as a therapeutic target in cholangiocarcinoma: mechanistic insights and translational implications.Cell & bioscience · 2025Article
- KDM4A regulates microglial polarization after ischemic stroke by regulating SPINK5 signaling.Acta biochimica et biophysica Sinica · 2025Article
- Epigenetic mechanisms of drug resistance in acute myeloid leukemia: advances in small-molecule targeted therapy.Frontiers in pharmacology · 2025Review
- PAF1/HIF1α axis rewires the glycolytic metabolism to fuel aggressiveness of pancreatic cancer.Cancer & metabolism · 2024Article
- The MYC-NFATC2 axis maintains the cell cycle and mitochondrial function in acute myeloid leukaemia cells.Molecular oncology · 2024Article
- The emerging roles of lysine-specific demethylase 4A in cancer: Implications in tumorigenesis and therapeutic opportunities.Genes & diseases · 2024Review
- Post-translational modifications of histones: Mechanisms, biological functions, and therapeutic targets.MedComm · 2023Review
- Enhancing HIV-1 latency reversal through regulating the elongating RNA Pol II pause-release by a small-molecule disruptor of PAF1C.Science advances · 2023Article
- KDM4 Demethylases: Structure, Function, and Inhibitors.Advances in experimental medicine and biology · 2023Article
- Comprehensive analyses of prognostic biomarkers and immune infiltrates among histone lysine demethylases (KDMs) in hepatocellular carcinoma.Cancer immunology, immunotherapy : CII · 2022Article
- Recent Advances with KDM4 Inhibitors and Potential Applications.Journal of medicinal chemistry · 2022Review
- Epigenetic Modification of PD-1/PD-L1-Mediated Cancer Immunotherapy against Melanoma.International journal of molecular sciences · 2022Review
- Transcriptomic and Drug Discovery Analyses Reveal Natural Compounds Targeting the KDM4 Subfamily as Promising Adjuvant Treatments in Cancer.Frontiers in genetics · 2022Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Epigenomic dysregulation is a common pathological feature in human hematological malignancies. H3K9me3 emerges as an important epigenomic marker in acute myeloid leukemia (AML). Its associated methyltransferases, such as SETDB1, suppress AML leukemogenesis, whilst H3K9me3 demethylases KDM4C is required for mixed-lineage leukemia rearranged AML. However, the specific role and molecular mechanism of action of another member of the KDM4 family, KDM4A has not previously been clearly defined. In this study, we delineated and functionally validated the epigenomic network regulated by KDM4A. We show that selective loss of KDM4A is sufficient to induce apoptosis in a broad spectrum of human AML cells. This detrimental phenotype results from a global accumulation of H3K9me3 and H3K27me3 at KDM4A targeted genomic loci thereby causing downregulation of a KDM4A-PAF1 controlled transcriptional program essential for leukemogenesis, distinct from that of KDM4C. From this regulatory network, we further extracted a KDM4A-9 gene signature enriched with leukemia stem cell activity; the KDM4A-9 score alone or in combination with the known LSC17 score, effectively stratifies high-risk AML patients. Together, these results establish the essential and unique role of KDM4A for AML self-renewal and survival, supporting further investigation of KDM4A and its targets as a potential therapeutic vulnerability in AML.
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