ArticleBlood cancer discovery2021
Lysine Demethylase 5A is Required for MYC Driven Transcription in Multiple Myeloma.
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Article in Blood cancer discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24 citing papers in PubMed, 39 citations in OpenAlex.
- Targeting the Chromatin-Modifying Enzyme, KDM5C, Enhances AKT Inhibition Response in ER+ Breast Cancer.Molecular cancer therapeutics · 2026Article
- Inhibition of KDM5A/B promotes antitumor innate immune responses in HHV-8/KSHV-positive B-cell lymphomas.Npj viruses · 2026Article
- A RIPK2 activity signature in prostate cancer: Modulation by RIPK2 inhibition and clinical association.Translational oncology · 2026Article
- Dual inhibition of KDM4B and KDM5A disassembles the PAX3-FOXO1 transcriptional program in fusion-positive rhabdomyosarcoma.Biology direct · 2026Article
- Inhibition of KDM5A/B promotes antitumor innate immune responses in HHV-8/KSHV-positive B-cell lymphomas.bioRxiv : the preprint server for biology · 2026Article
- SETD1A regulates psychiatric gene networks involved in genomic stability and synaptic function in rare and sporadic schizophrenia.Nature communications · 2025Article
- ZBTB7A is a modulator of KDM5-driven transcriptional networks in basal breast cancer.Cell reports · 2024Article
- Lysine and arginine methylation of transcription factors.Cellular and molecular life sciences : CMLS · 2024Review
- Epigenetic therapies targeting histone lysine methylation: complex mechanisms and clinical challenges.The Journal of clinical investigation · 2024Review
- SETD1B mutations confer apoptosis resistance and BCL2 independence in B cell lymphoma.The Journal of experimental medicine · 2024Article
- Drug tolerant persister cell plasticity in cancer: A revolutionary strategy for more effective anticancer therapies.Signal transduction and targeted therapy · 2024Review
- KDM5A/B contribute to HIV-1 latent infection and survival of HIV-1 infected cells.Antiviral research · 2024Article
- Targeting lysine demethylase 5 (KDM5) in mantle cell lymphoma.Blood cancer journal · 2024Article
- Domain architecture and protein-protein interactions regulate KDM5A recruitment to the chromatin.Epigenetics · 2023Review
- KDM5-mediated activation of genes required for mitochondrial biology is necessary for viability in Drosophila.Development (Cambridge, England) · 2023Article
- Review
- BRD9 Degradation Disrupts Ribosome Biogenesis in Multiple Myeloma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Proximity labeling reveals a new in vivo network of interactors for the histone demethylase KDM5.Epigenetics & chromatin · 2023Article
- KDM5 Lysine Demethylases in Pathogenesis, from Basic Science Discovery to the Clinic.Advances in experimental medicine and biology · 2023Article
- Elotuzumab, a potential therapeutic humanized anti-SLAMF7 monoclonal antibody, enhances natural killer cell-mediated killing of primary effusion lymphoma cells.Cancer immunology, immunotherapy : CII · 2022Article
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Authors and funding
30 authors at 9 institutions in 3 countries.
Hiroto Ohguchi *Division of Disease Epigenetics, Institute of Resource Development and Analysis, Kumamoto University, Kumamoto, Japan. ohguchi@kumamoto-u.ac.jp Kenneth_anderson@dfci.harvard.edu teru_hideshima@dfci.harvard.edu jun_qi@dfci.harvard.edu.
Paul M C Park *Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0002-9380-8548
Tingjian Wang *Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0003-2203-9590
Berkley E Gryder *Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.ORCID 0000-0003-0130-2302
Daisuke OgiyaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Keiji KurataDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Xiaofeng ZhangDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0003-4529-1158
Deyao LiDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Chengkui PeiDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Takeshi MasudaDepartment of Pharmaceutical Microbiology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.ORCID 0000-0003-0121-4783
Catrine JohanssonBotnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom.
Virangika K WimalasenaDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0002-1061-3439
Yong KimGenetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.ORCID 0000-0002-5417-9232
Shinjiro HinoDepartment of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
Shingo UsukiLiaison Laboratory Research Promotion Center, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
Yawara KawanoDepartment of Hematology, Rheumatology and Infectious Diseases, Kumamoto University School of Medicine, Kumamoto, Japan.ORCID 0000-0002-8269-440X
Mehmet K SamurDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Yu-Tzu TaiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0001-6199-3569
Nikhil C MunshiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Masao MatsuokaDepartment of Hematology, Rheumatology and Infectious Diseases, Kumamoto University School of Medicine, Kumamoto, Japan.ORCID 0000-0002-0473-754X
Sumio OhtsukiDepartment of Pharmaceutical Microbiology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.ORCID 0000-0003-4634-7133
Mitsuyoshi NakaoDepartment of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.ORCID 0000-0002-2196-8673
Takashi MinamiDivision of Molecular and Vascular Biology, Institute of Resource Development and Analysis, Kumamoto University, Kumamoto, Japan.ORCID 0000-0002-2345-1379
Shannon LauberthDivision of Biological Sciences, University of Califonia, San Diego, La Jolla, California.
Javed KhanGenetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Udo OppermannBotnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom.
Adam D DurbinDivision of Molecular Oncology, Department of Oncology, and Comprehensive Cancer Center, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0002-5472-9847
Kenneth C AndersonDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. ohguchi@kumamoto-u.ac.jp Kenneth_anderson@dfci.harvard.edu teru_hideshima@dfci.harvard.edu jun_qi@dfci.harvard.edu.
Teru HideshimaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. ohguchi@kumamoto-u.ac.jp Kenneth_anderson@dfci.harvard.edu teru_hideshima@dfci.harvard.edu jun_qi@dfci.harvard.edu.
Jun QiDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts. ohguchi@kumamoto-u.ac.jp Kenneth_anderson@dfci.harvard.edu teru_hideshima@dfci.harvard.edu jun_qi@dfci.harvard.edu.ORCID 0000-0002-1461-3356
Dana-Farber Cancer Institute · USKumamoto University · JPNational Institutes of Health · USHarvard University · USKumamoto Industrial Research Institute · JPKumamoto University Hospital · JPNuffield Orthopaedic Centre · GBSt. Jude Children's Research Hospital · USUniversity of California San Diego · US
Funding
Trageting the Multiple Myeloma EpigenomeP50CA100707 · NCI · DANA-FARBER CANCER INSTITUTE · PI ANDERSON, KENNETH C., MUNSHI, NIKHIL C. · 2003 to 2023
$45.0MTargeting Genomic Instability and Evolution in MyelomaP01CA155258 · NCI · DANA-FARBER CANCER INST · PI Jill Corre · 2011 to 2026
$32.5MCancer Chemical Biology and Metabolism Training ProgramT32CA236754 · NCI · DANA-FARBER CANCER INST · PI Nika N Danial, THOMAS M ROBERTS · 2019 to 2026
$2.6MTranscriptional and Epigenetic Adaptation as Novel Therapeutic Vulnerabilities for Mantle Cell LymphomaR01CA233601 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI DUCKETT, DEREK RONALD, QI, JUN · 2020 to 2024
$2.5MThe Roles of Enhancer RNAs in the Regulation of Gene ExpressionR35GM128900 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LAUBERTH, SHANNON MARIE · 2018 to 2022
$2.0MTargeting EP300, a selective dependency in neuroblastomaK08CA245251 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI DURBIN, ADAM DAVID · 2020 to 2024
$1.3MNCI NIH HHS K08 CA245251NCI NIH HHS P01 CA155258NCI NIH HHS P50 CA100707NCI NIH HHS R01 CA233601NCI NIH HHS T32 CA236754NIGMS NIH HHS R35 GM128900
Abstract
Lysine demethylase 5A (KDM5A) is a negative regulator of histone H3K4 trimethylation, a histone mark associated with activate gene transcription. We identify that KDM5A interacts with the P-TEFb complex and cooperates with MYC to control MYC targeted genes in multiple myeloma (MM) cells. We develop a cell-permeable and selective KDM5 inhibitor, JQKD82, that increases histone H3K4me3 but paradoxically inhibits downstream MYC-driven transcriptional output
Indexed as
LysineMultiple MyelomaCyclin-Dependent Kinase 9Cyclin-Dependent Kinase-Activating KinaseCyclin-Dependent KinasesGenes, cdcHumansMethylationProto-Oncogene Proteins c-mycRetinoblastoma-Binding Protein 2RNA Polymerase IICDK7 protein, humanCyclin-Dependent Kinase 9Cyclin-Dependent Kinase-Activating KinaseCyclin-Dependent KinasesKDM5A protein, humanLysineMYC protein, humanProto-Oncogene Proteins c-mycRetinoblastoma-Binding Protein 2RNA Polymerase IIEpigeneticsHistone modificationsJQKD82KDM5 inhibitorMultiple myelomaTranscription factor
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