ArticleNature cancer2024
Targeting PRMT9-mediated arginine methylation suppresses cancer stem cell maintenance and elicits cGAS-mediated anticancer immunity.
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Article in Nature cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31citing papers in PubMed
6.1field-weighted citation impact, top 3% of its field
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Who cites it
31 citing papers in PubMed, 26 citations in OpenAlex.
- Targeting PRMTs with small-molecule inhibitors: a comprehensive review.RSC medicinal chemistry · 2026Review
- cGAS-STING as a Neuroimmune Traffic Molecule: Unraveling Pathogenic Mechanisms and Therapeutic Potential in Neurological Disorders.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026Review
- Nanoparticle-based strategies targeting disulfidptosis, anoikis, and PANoptosis for enhanced cancer therapy.Journal of nanobiotechnology · 2026Review
- Inhibition of ADSS2-mediated de novo AMP biosynthesis re-sensitizes acute myeloid leukemia to BH3 mimetics.Nature cancer · 2026Article
- PRMT3-Mediated Arginine Methylation Stabilizes PCSK9 to Promote Aortic Valve Calcification.Circulation · 2026Article
- From Epigenetic Dysregulation to Therapeutic Reprogramming in Endometrial Cancer: A State-Response Framework for Treatment Resistance.International journal of molecular sciences · 2026Review
- Macrophage PRMT9 Ameliorates Acute Myocardial Infarction by Promoting Symmetric Dimethylation and Degradation of STAT1.Circulation · 2026Article
- New selective and allosteric FLT3 inhibitors show efficacy against resistant acute myeloid leukemia cells.iScience · 2026Article
- Protein arginine methyltransferases in cancer: mechanisms, functions, and therapeutic opportunities.Journal of biomedical science · 2026Review
- Advances in ligand-targeted nanodelivery systems for leukemia therapy: from single- to dual-ligand strategies.Journal of translational medicine · 2026Review
- PRMT3 Drives IDO1-Dependent Radioresistance and Immunosuppression by Promoting Kynurenine Metabolism in Non-Small Cell Lung Cancer.Cancer research · 2026Article
- PRMT5 inhibits the ferroptosis of hepatocellular carcinoma via regulating RBM15/FTH1 signaling.American journal of cancer research · 2026Article
- Amino acid metabolic regulatory network in tumor immune escape: mechanistic exploration and intervention directions.Frontiers in immunology · 2026Review
- Reimagining AHR in Cancer: From Environmental Sensor to Novel Immunomodulatory Therapeutic Target.International journal of biological sciences · 2026Review
- Arginine methylation in cancer: mechanisms and therapeutic implications.Biomarker research · 2025Review
- Turning cold tumors into hot tumors to ignite immunotherapy.Molecular cancer · 2025Review
- Current and Emerging Therapies for Targeting Protein Arginine Methyltransferases (PRMTs) in Cancer.International journal of molecular sciences · 2025Review
- Epigenetic regulation of cancer stemness.Signal transduction and targeted therapy · 2025Review
- Regulation of cGAS-STING signalling and its diversity of cellular outcomes.Nature reviews. Immunology · 2025Review
- Review
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Authors and funding
32 authors at 9 institutions in 2 countries.
Haojie Dong *Department of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA.
Xin He *Department of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA.
Lei Zhang *Department of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA.
Wei ChenIntegrative Genomics Core, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA.
Yi-Chun LinDepartment of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA, USA.
Song-Bai LiuSuzhou Key Laboratory of Medical Biotechnology, Suzhou Vocational Health College, Suzhou, People's Republic of China.ORCID 0000-0002-3920-1032
Huafeng WangDepartment of Hematology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
Le Xuan Truong NguyenDepartment of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA.
Min LiDivision of Biostatistics, Department of Computational and Quantitative Medicine, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA.
Yinghui ZhuDepartment of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA.
Dandan ZhaoDepartment of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA.
Lucy GhodaDepartment of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA.ORCID 0000-0002-8212-3586
Jonathan SerodyDepartment of Medicine, Division of Hematology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.ORCID 0000-0003-4568-1092
Benjamin VincentDepartment of Medicine, Division of Hematology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.ORCID 0000-0002-1762-2282
Leo LuznikDepartment of Oncology and Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Ivana GojoDepartment of Oncology and Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Joshua ZeidnerDepartment of Medicine, Division of Hematology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
Rui SuDepartment of Systems Biology, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA.ORCID 0000-0002-4807-6229
Jianjun ChenDepartment of Systems Biology, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA.ORCID 0000-0003-3749-2902
Ritin SharmaCancer & Cell Biology Division, The Translational Genomics Research Institute, Phoenix, AZ, USA.
Patrick PirrotteCancer & Cell Biology Division, The Translational Genomics Research Institute, Phoenix, AZ, USA.ORCID 0000-0003-1360-6039
Xiwei WuIntegrative Genomics Core, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA.
Weidong HuDepartment of Immunology and Theranostics, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA.
Weidong HanSir Run Run Shaw Hospital, Zhejiang University, Hangzhou, People's Republic of China.ORCID 0000-0001-7227-3671
Binghui ShenDepartment of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA.
Ya-Huei KuoDepartment of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA.ORCID 0000-0003-2595-0419
Jie JinDepartment of Hematology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
Amandeep SalhotraDepartment of Hematology and HCT, City of Hope Medical Center, Duarte, CA, USA.
Jeffrey WangDepartment of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA, USA.
Guido MarcucciDepartment of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA.ORCID 0000-0002-3983-5908
Yun Lyna LuoDepartment of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA, USA.
Ling LiDepartment of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, USA. lingli@coh.org.ORCID 0000-0001-7568-939X
City of Hope · USCity Of Hope National Medical Center · USUniversity of North Carolina at Chapel Hill · USWestern University of Health Sciences · USFirst Affiliated Hospital Zhejiang University · CNJohns Hopkins University · USTranslational Genomics Research Institute · USSir Run Run Shaw Hospital · CNSuzhou Vocational Health College · CN
Funding
Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI John Charles Williams · 1985 to 2026
$86.3MFunction Analysis of FEN-1 Nuclease in Genome StabilityR01CA073764 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI BINGHUI SHEN · 2002 to 2026
$7.9MThe role and therapeutic potential of IGF2BP2 in MLL-rearranged leukemiaR01CA271497 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI Jianjun Chen · 2022 to 2026
$2.8MTargeting FTO to treat acute myeloid leukemiaR01CA243386 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI CHEN, JIANJUN · 2020 to 2024
$2.8MTET2-mediated epitranscriptomic regulation in leukemia microenvironmentR01CA280389 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI Jianjun Chen · 2023 to 2026
$2.7MThe role and mechanism of METTL3/METTL14-mediated RNA modification in the pathogenesis and drug-resistance of AMLR01CA236399 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI CHEN, JIANJUN · 2019 to 2023
$2.3MTargeting protein acetylation as a therapeutic approach for MDSR01HL141336 · NHLBI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI LI, LING · 2018 to 2022
$2.2MTargeting Protein Arginine Methyltransferases to Eradicate Acute Myeloid LeukemiaR01CA279595 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI LING LI · 2024 to 2026
$2.1MRole of Protein Arginine Methyltransferase 9 in Acute Myeloid Leukemia MaintenanceR01CA248149 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI LI, LING · 2020 to 2024
$2.1MNCI NIH HHS P30 CA033572NCI NIH HHS R01 CA073764NCI NIH HHS R01 CA236399NCI NIH HHS R01 CA243386NCI NIH HHS R01 CA248149NCI NIH HHS R01 CA271497NCI NIH HHS R01 CA279595NCI NIH HHS R01 CA280389NHLBI NIH HHS R01 HL141336NIH HHS ACS RSG-19-036001-LIB
Abstract
Current anticancer therapies cannot eliminate all cancer cells, which hijack normal arginine methylation as a means to promote their maintenance via unknown mechanisms. Here we show that targeting protein arginine N-methyltransferase 9 (PRMT9), whose activities are elevated in blasts and leukemia stem cells (LSCs) from patients with acute myeloid leukemia (AML), eliminates disease via cancer-intrinsic mechanisms and cancer-extrinsic type I interferon (IFN)-associated immunity. PRMT9 ablation in AML cells decreased the arginine methylation of regulators of RNA translation and the DNA damage response, suppressing cell survival. Notably, PRMT9 inhibition promoted DNA damage and activated cyclic GMP-AMP synthase, which underlies the type I IFN response. Genetically activating cyclic GMP-AMP synthase in AML cells blocked leukemogenesis. We also report synergy of a PRMT9 inhibitor with anti-programmed cell death protein 1 in eradicating AML. Overall, we conclude that PRMT9 functions in survival and immune evasion of both LSCs and non-LSCs; targeting PRMT9 may represent a potential anticancer strategy.
Indexed as
ArginineLeukemia, Myeloid, AcuteNeoplastic Stem CellsNucleotidyltransferasesProtein-Arginine N-MethyltransferasesAnimalsCell Line, TumorCell SurvivalCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseDNA DamageHumansInterferon Type IMethylationMiceArgininecGAS protein, humanCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseInterferon Type INucleotidyltransferasesProtein-Arginine N-Methyltransferases
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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 Socratic graph.