PXD035635 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Epigenetic Control over IFN Type-I Response antagonizes self-renewal in acute myeloid leukemia |
Description | Large biological heterogeneity hallmarks acute myeloid leukemia (AML) and substantially hampers development of novel comprehensive therapies. While all-trans retinoic acid (ATRA) revolutionized therapy of acute promyelocytic leukemia, its impact on other AML subtypes remained largely disappointing. Here we show for the first time that ATRA mediated phosphorylation of the histone demethylase PHF8 induces apoptosis of AML cells of different subtypes via regulation of viral mimicry and subsequent initiation of interferon (IFN) type-I response. Phospho-PHF8 conferred H3K9me2 demethylation at promoter sites of key initiators of cell-intrinsic immune response. Multiomics based analyses revealed activation of cytosolic RNA sensors as key step towards NF-κB driven IFN type-I mediated apoptosis. Epigenetic changes directed by PHF8 also induced a specific proteosome pathway controlling NF-κB activity after its initial activation. Hence, PHF8 orchestrates viral mimicry, triggering IFN type-I response-differentiation-apoptotic network in a broad spectrum of AML when activated by ATRA. Forced phosphorylation of PHF8 via combination treatment with ATRA and simultaneous pharmacological inhibition of PHF8 dephosphorylation significantly impaired growth of human AML. Our findings finally open the gate for successful application of ATRA-based combination therapies in AML. |
HostingRepository | PRIDE |
AnnounceDate | 2024-06-22 |
AnnouncementXML | Submission_2024-06-22_11:22:32.193.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Ashokkumar Jayavelu |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | phosphorylated residue |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-07-29 09:01:26 | ID requested | |
⏵ 1 | 2024-06-22 11:22:33 | announced | |
Publication List
Felipe Fumero E, Walter C, Frenz JM, Seifert F, Alla V, Hennig T, Angenendt L, Hartmann W, Wolf S, Serve H, Oellerich T, Lenz G, M, ü, ller-Tidow C, Schliemann C, Huber O, Dugas M, Mann M, Jayavelu AK, Mikesch JH, Arteaga MF, Epigenetic control over the cell-intrinsic immune response antagonizes self-renewal in acute myeloid leukemia. Blood, 143(22):2284-2299(2024) [pubmed] |
10.1182/blood.2023021640; |
Keyword List
submitter keyword: AML, PHF8, ATRA, Proteome, Phosphoproteome |
Contact List
Dr.Ashok Kumar Jayavelu |
contact affiliation | Proteomics and Cancer Cell Signaling Unit, German Cancer Research center(DKFZ), Heidelberg, Germany |
contact email | ak.jayavelu@dkfz-heidelberg.de |
lab head | |
Ashokkumar Jayavelu |
contact affiliation | Dept Proteomics and Signal Transduction, MaxPlanck Institute of Biochemistry |
contact email | jayavelu@biochem.mpg.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD035635
- Label: PRIDE project
- Name: Epigenetic Control over IFN Type-I Response antagonizes self-renewal in acute myeloid leukemia