PXD058286 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | The Histone Acetyltransferase MOZ is a Molecular Dependency and Therapeutic Target in NUP98-Rearranged Acute Myeloid Leukemia |
Description | NUP98 fusion oncoproteins (FOs) are a hallmark of childhood acute myeloid leukemia (AML), and drive leukemogenesis through liquid-liquid phase separation-mediated nuclear condensate formation. However, the composition and consequences of NUP98 FO-associated condensates are incompletely understood. Here we show that histone acetyltransferase (HAT) complex proteins including MOZ associate with NUP98 FOs, and that BRPF1, an epigenetic writer that associates with MOZ is a molecular dependency in NUP98::KDM5A AML. Inactivation of Brpf1 as well as HAT complex member Moz, Hbo1, Brd1 or Meaf6 in Nup98::Kdm5a;Vav-Cre cells impaired fitness of NUP98-rearranged cells. MOZ inhibition decreased global H3K23ac levels, displaced FO from chromatin at the Meis1 locus, and led to myeloid cell differentiation. Additionally, MOZ inhibition decreased leukemic burden in multiple NUP98-rearranged leukemia xenograft models, synergized with Menin inhibitor treatment, and was efficacious in Menin inhibitor-resistant cells. In summary, we show that MOZ is a potentially targetable dependency in NUP98-rearranged AMLs. SIGNIFICANCE STATEMENT MOZ is a member of NUP98 FO condensates with key roles in leukemia phenotypes. MOZ inhibition is effective in multiple preclinical models, including those non-responsive to Menin inhibition. MOZ and Menin inhibition are synergistic in some NUP98-rearranged models, supporting clinical translation to improve outcomes of NUP98 FO-driven leukemias. |
HostingRepository | PRIDE |
AnnounceDate | 2025-06-03 |
AnnouncementXML | Submission_2025-06-03_08:28:08.048.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Valar Nila Roamio Franklin |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; deaminated residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-11-26 04:53:17 | ID requested | |
⏵ 1 | 2025-06-03 08:28:08 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: histone acetyltransferase, gene fusion, leukemia,NUP98 |
Contact List
Clive D'santos |
contact affiliation | Head of the Department, Proteomics Core |
contact email | clivesdsantos@gmail.com |
lab head | |
Valar Nila Roamio Franklin |
contact affiliation | Principal Scientific Associate |
contact email | Valar.Franklin@cruk.cam.ac.uk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD058286
- Label: PRIDE project
- Name: The Histone Acetyltransferase MOZ is a Molecular Dependency and Therapeutic Target in NUP98-Rearranged Acute Myeloid Leukemia