Hotspot DNA Methyltransferase 3A (DNMT3A) and Isocitrate Dehydrogenase 1 and 2 (IDH1/2) Mutations in Acute Myeloid Leukemia and Their Relevance as Targets for Immunotherapy.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38791049", "kind": "science-record", "revision": 4, "content_hash": "sha256:2475e319a6e3c7fedd5cf079c1d23c0595355dace2d54fec4b650b0d54ad7dbb", "created_at": "2026-11-01T19:20:44Z", "updated_at": "2026-11-01T22:11:55Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Hotspot DNA Methyltransferase 3A (DNMT3A) and Isocitrate Dehydrogenase 1 and 2 (IDH1/2) Mutations in Acute Myeloid Leukemia and Their Relevance as Targets for Immunotherapy.", "doi": "10.3390/biomedicines12051086", "pmid": "38791049", "authors": ["Nadine E Struckman", "Rob C M de Jong", "M Willy Honders", "Sophie-Anne I Smith", "Dyantha I van der Lee", "Georgia Koutsoumpli", "Arnoud H de Ru", "Jan-Henrik Mikesch", "Peter A van Veelen", "J H Frederik Falkenburg", "Marieke Griffioen"], "journal": "Biomedicines", "year": 2024, "abstract": "DNA methyltransferase 3A (DNMT3A) and isocitrate dehydrogenase 1 and 2 (IDH1/2) are genes involved in epigenetic regulation, each mutated in 7-23% of patients with acute myeloid leukemia. Here, we investigated whether hotspot mutations in these genes encode neoantigens that can be targeted by immunotherapy. Five human B-lymphoblastoid cell lines expressing common HLA class I alleles were transduced with a minigene construct containing mutations that often occur in DNMT3A or IDH1/2. From these minigene-transduced cell lines, peptides were eluted from HLA class I alleles and analyzed using tandem mass spectrometry. The resulting data are available via ProteomeXchange under the identifier PXD050560. Mass spectrometry revealed an HLA-A*01:01-binding DNMT3AR882H peptide and an HLA-B*07:02-binding IDH2R140Q peptide as potential neoantigens. For these neopeptides, peptide-HLA tetramers were produced to search for specific T-cells in healthy individuals. 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-derived acute myeloid leukemia cells with the mutation, while patient samples without the mutation were not recognized, thereby validating the surface presentation of a DNMT3AR882H neoantigen that can potentially be targeted in acute myeloid leukemia via immunotherapy.", "claims": [{"id": "claim-method", "statement": "The mean numbers of alive cells after the co-incubation killing assays were compared with unpaired t-tests adjusted for multiple comparison according to the Benjamini method.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38791049", "locator": "sections[11] \"2.9. Statistical Analyses\" paragraph 2", "quote": "The mean numbers of alive cells after the co-incubation killing assays were compared with unpaired t-tests adjusted for multiple comparison according to the Benjamini method."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The mass spectrometry proteomics data have been deposited in the ProteomeXchange Consortium via the PRIDE [1] partner repository under the dataset identifier PXD050560.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38791049", "locator": "sections[24] \"Data Availability Statement\" paragraph 2", "quote": "The mass spectrometry proteomics data have been deposited in the ProteomeXchange Consortium via the PRIDE [1] partner repository under the dataset identifier PXD050560."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Mass spectrometry revealed an HLA-A*01:01-binding DNMT3AR882H peptide and an HLA-B*07:02-binding IDH2R140Q peptide as potential neoantigens.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38791049", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Mass spectrometry revealed an HLA-A*01:01-binding DNMT3AR882H peptide and an HLA-B*07:02-binding IDH2R140Q peptide as potential neoantigens."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Mass spectrometry revealed an HLA-A*01:01-binding DNMT3AR882H peptide and an HLA-B*07:02-binding IDH2R140Q peptide as potential neoantigens.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:38791049"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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