ArticleBlood2022
PLCG1 is required for AML1-ETO leukemia stem cell self-renewal.
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Article in Blood, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16citing papers in PubMed
2.8field-weighted citation impact, top 9% of its field
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Comutation of asxl1 and IDH2R172K enhances leukemogenesis and correlates with epigenetic activation of MAPK and AP-1 in zebrafish.Blood advances · 2026Article
- Integrated analysis of post-transcriptional regulations reveals insights into acute myeloid leukemia.Communications biology · 2025Article
- How to drug a leukemic stem cell: deciphering heterogeneity for better specificity.Blood neoplasia · 2025Review
- Integrated Network Pharmacology, Molecular Modeling, LC-MS Profiling, and Semisynthetic Approach for the Roots ofACS omega · 2025Article
- Impaired degradation of PLCG1 by chaperone-mediated autophagy promotes cellular senescence and intervertebral disc degeneration.Autophagy · 2025Article
- High glucose-induced PLCG1 histone acetylation to promote ferroptosis by LAMP2A/HSPA8 in a diabetic nephropathy model.Frontiers in pharmacology · 2025Article
- Glucocorticoids paradoxically promote steroid resistance in B cell acute lymphoblastic leukemia through CXCR4/PLC signaling.Nature communications · 2024Article
- Signaling pathways governing the behaviors of leukemia stem cells.Genes & diseases · 2024Review
- Leukemic stem cells activate lineage inappropriate signalling pathways to promote their growth.Nature communications · 2024Article
- Immunoproteasome function maintains oncogenic gene expression in KMT2A-complex driven leukemia.Molecular cancer · 2023Article
- Article
- Cryptic mutations of PLC family members in brain disorders: recent discoveries and a deep-learning-based approach.Brain : a journal of neurology · 2023Review
- Article
- A scoring system based on fusion genes to predict treatment outcomes of the non-acute promyelocytic leukemia pediatric acute myeloid leukemia.Frontiers in medicine · 2023Article
- Context-specific effects of NOX4 inactivation in acute myeloid leukemia (AML).Journal of cancer research and clinical oncology · 2022Article
- Proteomic analysis reveals dual requirement for Grb2 and PLCγ1 interactions for BCR-FGFR1-Driven 8p11 cell proliferation.Oncotarget · 2022Article
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Authors and funding
37 authors at 18 institutions in 7 countries.
Tina M SchnoederInnere Medizin C, Hämatologie, Onkologie, Stammzelltransplantation und Palliativmedizin, Universitätsmedizin Greifswald, Greifswald, Germany.
Adrian SchwarzerDepartment of Hematology, Hemostaseology, Oncology and Stem Cell Transplantation, and.
Ashok Kumar JayaveluMax-Planck-Institute of Biochemistry, Munich, Germany.
Chen-Jen HsuInnere Medizin C, Hämatologie, Onkologie, Stammzelltransplantation und Palliativmedizin, Universitätsmedizin Greifswald, Greifswald, Germany.
Joanna KirkpatrickLeibniz Institute on Aging, Fritz-Lipmann Institute (FLI), Jena, Germany.ORCID 0000-0001-9291-7294
Konstanze DöhnerDepartment of Internal Medicine III, University Hospital Ulm, Ulm, Germany.
Florian PernerInnere Medizin C, Hämatologie, Onkologie, Stammzelltransplantation und Palliativmedizin, Universitätsmedizin Greifswald, Greifswald, Germany.
Theresa EifertInnere Medizin C, Hämatologie, Onkologie, Stammzelltransplantation und Palliativmedizin, Universitätsmedizin Greifswald, Greifswald, Germany.
Nicolas HuberInnere Medizin C, Hämatologie, Onkologie, Stammzelltransplantation und Palliativmedizin, Universitätsmedizin Greifswald, Greifswald, Germany.
Patricia Arreba-TutusausDepartment of Oncology, Hematology, Immunology, and Rheumatology, University Hospital Tübingen, Tübingen, Germany.
Anna DolnikHematology, Oncology and Tumor Immunology, Charité University Medicine, Berlin, Germany.
Salam A AssiInstitute for Cancer and Genomic Sciences, University of Birmingham, Birmingham, United Kingdom.ORCID 0000-0001-5634-1347
Monica NafriaInstitute for Cancer and Genomic Sciences, University of Birmingham, Birmingham, United Kingdom.ORCID 0000-0002-5329-7966
Lu JiangState Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine, Ruijin Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yu-Ting DaiState Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine, Ruijin Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China.ORCID 0000-0001-8275-2115
Zhu ChenState Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine, Ruijin Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Sai-Juan ChenState Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine, Ruijin Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Sophie G KellawayInstitute for Cancer and Genomic Sciences, University of Birmingham, Birmingham, United Kingdom.ORCID 0000-0002-4011-7460
Anetta PtasinskaInstitute for Cancer and Genomic Sciences, University of Birmingham, Birmingham, United Kingdom.
Elizabeth S NgMurdoch Children's Research Institute, The Royal Children's Hospital, Parkville, VIC, Australia.ORCID 0000-0002-7970-8129
Edouard G StanleyMurdoch Children's Research Institute, The Royal Children's Hospital, Parkville, VIC, Australia.
Andrew G ElefantyMurdoch Children's Research Institute, The Royal Children's Hospital, Parkville, VIC, Australia.ORCID 0000-0001-6448-8314
Marcus BuschbeckJosep Carreras Leukemia Research Institute, Badalona, Spain.
Holger BierhoffInstitute of Biochemistry and Biophysics, Center for Molecular Biomedicine, Friedrich-Schiller University, Jena, Germany.
Steffen BrodtUniversity Hospital Jena, Orthopaedic Department at Campus Eisenberg, Eisenberg, Germany.ORCID 0000-0003-1286-8766
Georg MatziolisUniversity Hospital Jena, Orthopaedic Department at Campus Eisenberg, Eisenberg, Germany.
Klaus-Dieter FischerInstitute for Cell Biology and Biochemistry, Otto-von-Guericke University, Magdeburg, Germany.
Andreas HochhausInnere Medizin 2, Hämatologie und Onkologie, Universitätsklinikum Jena, Germany.
Chun-Wei ChenDepartment of Systems Biology, Beckman Research Institute of City of Hope, Duarte, CA.ORCID 0000-0002-8737-6830
Olaf HeidenreichNorthern Institute for Cancer Research, University of Newcastle, Newcastle upon Tyne, United Kingdom.ORCID 0000-0001-5404-6483
Matthias MannMax-Planck-Institute of Biochemistry, Munich, Germany.
Steven W LaneQIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.ORCID 0000-0002-8050-6209
Lars BullingerHematology, Oncology and Tumor Immunology, Charité University Medicine, Berlin, Germany.
Alessandro OriLeibniz Institute on Aging, Fritz-Lipmann Institute (FLI), Jena, Germany.ORCID 0000-0002-3046-0871
Björn von EyssLeibniz Institute on Aging, Fritz-Lipmann Institute (FLI), Jena, Germany.ORCID 0000-0002-4731-6841
Constanze BoniferInstitute for Cancer and Genomic Sciences, University of Birmingham, Birmingham, United Kingdom.
Florian H HeidelInnere Medizin C, Hämatologie, Onkologie, Stammzelltransplantation und Palliativmedizin, Universitätsmedizin Greifswald, Greifswald, Germany.ORCID 0000-0003-2438-1955
Universitätsmedizin Greifswald · DEUniversity of Birmingham · GBShanghai Jiao Tong University · CNLeibniz Institute on Aging - Fritz Lipmann Institute (FLI) · DERoyal Children's Hospital · AUCharité - Universitätsmedizin Berlin · DEMax Planck Institute of Biochemistry · DECity of Hope · USFriedrich Schiller University Jena · DEHarvard University · USJena University Hospital · DEJosep Carreras Leukaemia Research Institute · ESMedizinische Hochschule Hannover · DEOtto-von-Guericke-Universität Magdeburg · DEPrincess Máxima Center · NLQIMR Berghofer Medical Research Institute · AUUniversity Children's Hospital Tübingen · DEUniversity Hospital Ulm · DE
Funding
Combinational Targeting the Feed-forward Epigenetic Circuitry in Mixed Lineage LeukemiaR37CA233691 · NCI · MAYO CLINIC ROCHESTER · PI CHEN, CHUN-WEI DAVID · 2019 to 2025
$2.8MRole of BAZ2A in MLL-r leukemia and therapeutic responseR01CA236626 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI CHEN, CHUN-WEI DAVID · 2019 to 2023
$2.2MMedical Research Council MR/S021469/1NCI NIH HHS R01 CA236626NCI NIH HHS R37 CA233691
Abstract
In an effort to identify novel drugs targeting fusion-oncogene-induced acute myeloid leukemia (AML), we performed high-resolution proteomic analysis. In AML1-ETO (AE)-driven AML, we uncovered a deregulation of phospholipase C (PLC) signaling. We identified PLCgamma 1 (PLCG1) as a specific target of the AE fusion protein that is induced after AE binding to intergenic regulatory DNA elements. Genetic inactivation of PLCG1 in murine and human AML inhibited AML1-ETO dependent self-renewal programs, leukemic proliferation, and leukemia maintenance in vivo. In contrast, PLCG1 was dispensable for normal hematopoietic stem and progenitor cell function. These findings are extended to and confirmed by pharmacologic perturbation of Ca++-signaling in AML1-ETO AML cells, indicating that the PLCG1 pathway poses an important therapeutic target for AML1-ETO+ leukemic stem cells.
Indexed as
Gene Expression Regulation, LeukemicAnimalsCell Self RenewalCore Binding Factor Alpha 2 SubunitHematopoietic Stem CellsHumansLeukemia, Myeloid, AcuteMiceNeoplastic Stem CellsOncogene Proteins, FusionPhospholipase C gammaProteomeRUNX1 Translocation Partner 1 ProteinTranscriptomeTranslocation, GeneticAML1-ETO fusion protein, humanCore Binding Factor Alpha 2 SubunitOncogene Proteins, FusionPhospholipase C gammaPLCG1 protein, humanProteomeRUNX1 Translocation Partner 1 Protein
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