ArticleCancer discovery2025
KAT6A and KAT7 Histone Acetyltransferase Complexes Are Molecular Dependencies and Therapeutic Targets in NUP98-Rearranged Acute Myeloid Leukemia.
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Article in Cancer discovery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Nucleoporins in Cancer: Functional Roles and Therapeutic Opportunities.Cancer discovery · 2026Article
- The effect of cohesin mutations on HLA-class II expression in the myeloid leukemia of Down syndrome.Leukemia · 2026Article
- Condensates in fusion oncoprotein-driven leukemia: new biology and therapeutic opportunities.Trends in cancer · 2026Review
- Beyond nuclear export: chromatin-bound XPO1/CRM1 as a transcriptional scaffold.International journal of hematology · 2026Review
- Menin inhibitors as a treatment for acute leukemia: from bench to the clinic.Blood neoplasia · 2026Review
- Mesenchymal stromal/stem cells in tumour initiation, progression and therapy.Nature reviews. Cancer · 2026Review
- Advances in targeted therapies for pediatric tumors.Acta pharmacologica Sinica · 2026Article
- Preferential formation of NUP98-KDM5A condensates at specific H3K4me3-rich loci drives leukemogenic gene expression.bioRxiv : the preprint server for biology · 2026Article
- LncRNA FAM30A as a potential biomarker associated with periodontitis and its role in inflammatory responses and osteogenesis.BMC oral health · 2026Article
- Inhibition of histone acetyltransferase KAT7 suppresses proliferation and migration of breast cancer cells.Frontiers in oncology · 2026Article
- Functional Mapping of Epigenomic Regulators Uncovers Coordinated Tumor Suppression by the HBO1 and MLL1 Complexes.Cancer discovery · 2025Article
- Lysine Acetyltransferase 6 in Health and Disease.MedComm · 2025Review
- A new KAT on the block rewrites the epigenetic script in menin inhibitor-resistant leukemia.HemaSphere · 2025Article
- KMT2A-rearranged leukemia: from mechanism to drug development.Experimental hematology · 2025Review
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- Emerging strategies and novel therapeutic targets in acute myeloid leukemia: current advances and future directions.Biomarker research · 2025Review
- BRPF1 in cancer epigenetics: a key regulator of histone acetylation and a promising therapeutic target.Cell death discovery · 2025Review
- Combined inhibition of KAT6A/B and Menin reverses estrogen receptor-driven gene expression programs in breast cancer.Cell reports. Medicine · 2025Article
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Authors and funding
42 authors.
Nicole L Michmerhuizen *Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0002-9960-5119
Emily B Heikamp *Division of Hematology/Oncology, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-4591-4477
Ilaria IacobucciDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0003-2008-1365
Masayuki UmedaDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0009-0002-5636-6602
Bright ArthurDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0009-0002-7935-9712
Vibhor MishraDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0002-4846-4790
Chun Shik ParkDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0002-4329-3953
Danika Di GiacomoDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0002-5558-7967
Ryan HiltenbrandDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0002-9267-9844
Qingsong GaoDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0002-9930-8499
Sandi Radko-JuettnerDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0002-6969-5184
Josi LottDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0009-0004-2504-8657
Cynthia MartucciDivision of Hematology/Oncology, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0001-6126-9458
Varsha SubramanyamDivision of Hematology/Oncology, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts.ORCID 0009-0001-0205-3910
Charlie HattonDivision of Hematology/Oncology, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0001-9903-4291
Daniela V WengeDivision of Hematology/Oncology, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-0064-9104
Pradyuamna BaviskarDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0003-1110-5695
Pablo PortolaDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0009-0005-2990-0939
Aurelie ClaquinDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0009-0002-2962-6122
Bappaditya ChandraDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0001-7595-937X
David W BaggettDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0001-7437-1603
Ali KhalighifarCenter for Bioimage Informatics, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0002-2949-8143
Hongling HuangDepartment of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0009-0003-2655-399X
Peipei ZhouDepartment of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0001-9033-2559
Lingyun LongDepartment of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0002-8064-832X
Hao ShiDepartment of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0002-2796-629X
Yu SunDepartment of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0009-0002-3927-1396
Evangelia K PapachristouCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom.ORCID 0000-0002-5835-2055
Chandra Sekhar Reddy ChilamakuriCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom.ORCID 0009-0003-6434-7388
Francisca N de Luna VitorinoDepartment of Biochemistry and Molecular Biophysics, Washington University in St. Louis, St. Louis, Missouri.ORCID 0000-0001-8543-2299
Joanna M GongoraDepartment of Biochemistry and Molecular Biophysics, Washington University in St. Louis, St. Louis, Missouri.ORCID 0009-0006-7613-8219
Huiyun WuDepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0003-2728-4608
Stanley B PoundsDepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0002-9167-2114
Laura J JankeDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0002-9871-6239
Alex KentsisTow Center for Developmental Oncology, Molecular Pharmacology Program, Sloan Kettering Institute, New York, New York.ORCID 0000-0002-8063-9191
Clive S D'SantosCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom.ORCID 0000-0003-4592-0487
Benjamin A GarciaDepartment of Biochemistry and Molecular Biophysics, Washington University in St. Louis, St. Louis, Missouri.ORCID 0000-0003-3596-4750
Richard W KriwackiDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0002-9798-6018
Hongbo ChiDepartment of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0002-9997-2496
Jeffery M KlcoDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0003-2961-6960
Scott A ArmstrongDivision of Hematology/Oncology, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-9099-4728
Charles G MullighanDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.ORCID 0000-0002-1871-1850
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4MVectorP30CA006516 · NCI · DANA-FARBER CANCER INSTITUTE · PI Irene M. Ghobrial · 1985 to 2026
$330.6MViral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Shondra Michelle Miller · 1985 to 2026
$166.9MTYROSINE KINASE ONCOGENESIS IN MYELOID LEUKEMIAP01CA066996 · NCI · DANA-FARBER CANCER INSTITUTE · PI SCOTT A ARMSTRONG · 1996 to 2026
$52.5MTranslating genomic discoveries to improved outcomes for high risk acute leukemiaR35CA197695 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Charles G Mullighan · 2017 to 2026
$11.4MProject 4U54CA243124 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI MULLIGHAN, CHARLES G. · 2019 to 2023
$10.5MLAMPSP01CA298963 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Jian Xu · 2025 to 2026
$9.1MIntegrating systems immunology with immunometabolism and cancer immunityR35CA253188 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Hongbo Chi · 2021 to 2026
$6.0MABERRANT SIGNALING IN ACUTE MYELOID LEUKEMIAR01CA204396 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI KENTSIS, ALEX · 2016 to 2025
$5.2MRole of Phase separation by fusion oncoproteins in oncogenesisR01CA246125 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI DENIZ, ASHOK A, KRIWACKI, RICHARD W · 2020 to 2024
$3.2MChildhood Hematological Malignancies Training ProgramT32CA236748 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Charles G Mullighan · 2019 to 2026
$2.0MDefining epigenetic mechanisms in NPM1c mutant leukemiaR01CA259273 · NCI · DANA-FARBER CANCER INST · PI ARMSTRONG, SCOTT A · 2021 to 2025
$2.0MAmerican Society of Hematology (ASH)Burroughs Wellcome Fund (BWF)Center for Cancer Research (CCR) CA279891-01A1Center for Cancer Research (CCR) P30 CA06516Center for Cancer Research (CCR) T32 CA236738Charles H. Hood Foundation (CHF)Hyundai Hope On Wheels (Hope On Wheels)Leukemia and Lymphoma Society (LLS)NCI NIH HHS F32 CA261011NCI NIH HHS K08 CA279891NCI NIH HHS K99 CA283256NCI NIH HHS P01 CA066996NCI NIH HHS P01 CA298963NCI NIH HHS P30 CA006516NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA021765NCI NIH HHS R01 CA204396NCI NIH HHS R01 CA246125NCI NIH HHS R01 CA259273NCI NIH HHS R35 CA197695NCI NIH HHS R35 CA253188NCI NIH HHS T32 CA236748NCI NIH HHS U54 CA243124St. Jude Children's Research Hospital
Abstract
NUP98 fusion oncoproteins (FO) are a hallmark of childhood acute myeloid leukemia. NUP98 FOs drive leukemogenesis through phase-separated condensate formation and maintenance of an active chromatin landscape at stem cell-associated genes in cooperation with epigenetic regulators. In this study, we show that MYST family histone acetyltransferase (HAT) complex proteins, including KAT6A/MOZ, KAT7/HBO1, and the common KAT6A/7 complex subunit BRPF1, associate with NUP98 FOs on chromatin and within condensates. MYST HATs are molecular dependencies in NUP98-rearranged (NUP98-r) leukemia, and genetic inactivation or pharmacologic inhibition of KAT6A and KAT7 impairs NUP98-r cell fitness. KAT6A/7 inhibition decreased global H3K23ac levels, displaced NUP98::HOXA9 from chromatin at the Meis1 locus, and led to myeloid cell differentiation. Additionally, KAT6A/7 inhibition decreased leukemic burden in multiple NUP98-r leukemia xenograft mouse models, synergized with menin inhibitor treatment, and was efficacious in menin inhibitor-resistant cells. In summary, we show that MYST family HATs are therapeutically actionable dependencies in NUP98-r acute myeloid leukemia. SIGNIFICANCE: KAT6A and KAT7 associate with NUP98 FOs to drive leukemogenesis. Inhibition of their HAT activity is an effective therapeutic strategy in NUP98-r leukemias, including those resistant to menin inhibition. Moreover, combined KAT6A/7 and menin inhibition is synergistic, supporting clinical translation to improve outcomes for NUP98 FO-driven leukemias.
Indexed as
Histone AcetyltransferasesLeukemia, Myeloid, AcuteNuclear Pore Complex ProteinsOncogene Proteins, FusionAnimalsCell Line, TumorHumansMiceXenograft Model Antitumor AssaysHistone AcetyltransferasesKAT6A protein, humanKAT7 protein, humanNuclear Pore Complex ProteinsNup98 protein, humanOncogene Proteins, Fusion
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