| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Biomedicines, Vol 12, Iss 5, p 1086 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2227-9059 |
| DOI: |
10.3390/biomedicines12051086 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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