PXD050560 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Hotspot DNMT3A and IDH1/2 Mutations in Acute Myeloid Leukemia and Their Relevance as Targets for Immunotherapy |
Description | DNA methyltransferase 3A (DNMT3A) and isocitrate dehydrogenase 1 & 2 (IDH1/2) are genes involved in epigenetic regulation, each mutated in 7-23% of acute myeloid leukemia (AML). Here, we investigated whether hotspot mutations in these genes encode neoantigens that can be targeted by immunotherapy. Five EBV-B cell lines expressing common HLA class I alleles were transduced with a minigene construct containing mutations that often occur in DNMT3A or IDH1/2. Peptides eluted from HLA class I alleles on these EBV-B cell lines were analyzed by tandem mass spec-trometry. We identified an HLA-A*01:01-binding DNMT3AR882H peptide and HLA-B*07:02-binding IDH2R140Q peptide, for which we searched for specific T cells in healthy individuals using pep-tide-HLA tetramers. Various T-cell clones were isolated showing specific reactivity against cell lines transduced with full-length DNMT3AR882H or IDH2R140Q genes, while cell lines transduced with wildtype genes were not recognized. One T-cell clone for DNMT3AR882H also reacted against patient AML cells with the mutation, while AML cells without the mutation were not recognized, thereby validating surface presentation of a DNMT3AR882H neoantigen that can potentially be targeted on HLA-A*01:01 positive AML by immunotherapy. |
HostingRepository | PRIDE |
AnnounceDate | 2024-06-23 |
AnnouncementXML | Submission_2024-06-23_02:17:54.745.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Rayman Tjokrodirijo |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Orbitrap Fusion Lumos; Orbitrap Exploris 480 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-03-12 11:25:04 | ID requested | |
⏵ 1 | 2024-06-23 02:17:55 | announced | |
Publication List
Struckman NE, de Jong RCM, Honders MW, Smith SI, van der Lee DI, Koutsoumpli G, de Ru AH, Mikesch JH, van Veelen PA, Falkenburg JHF, Griffioen M, ) Mutations in Acute Myeloid Leukemia and Their Relevance as Targets for Immunotherapy. Biomedicines, 12(5):(2024) [pubmed] |
10.3390/biomedicines12051086; |
Keyword List
submitter keyword: hotspot mutation, iso-citrate dehydrogenase 2, DNA methyltransferase 3A,cancer immunotherapy, acute myeloid leukemia, neoantigen, T-cell therapy |
Contact List
Peter A. |
contact affiliation | Head Proteomics Group , Leiden University Medical Center, Center for Proteomics and Metabolomics, PO Box 9600, Postal zone P1-Q, 2300 RC Leiden, The Netherlands |
contact email | P.A.van_Veelen@lumc.nl |
lab head | |
Rayman Tjokrodirijo |
contact affiliation | Leiden University Medical Center, Proteomics group |
contact email | R.T.N.Tjokrodirijo@lumc.nl |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD050560
- Label: PRIDE project
- Name: Hotspot DNMT3A and IDH1/2 Mutations in Acute Myeloid Leukemia and Their Relevance as Targets for Immunotherapy