| Autor: |
Eline J. M. Bertrums, Jurrian K. de Kanter, Lucca L. M. Derks, Mark Verheul, Laurianne Trabut, Markus J. van Roosmalen, Henrik Hasle, Evangelia Antoniou, Dirk Reinhardt, Michael N. Dworzak, Nora Mühlegger, Marry M. van den Heuvel-Eibrink, C. Michel Zwaan, Bianca F. Goemans, Ruben van Boxtel |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Nature Communications, Vol 15, Iss 1, Pp 1-16 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-024-50384-z |
| Popis: |
Abstract Therapy-related myeloid neoplasms (t-MN) arise as a complication of chemo- and/or radiotherapy. Although t-MN can occur both in adult and childhood cancer survivors, the mechanisms driving therapy-related leukemogenesis likely vary across different ages. Chemotherapy is thought to induce driver mutations in children, whereas in adults pre-existing mutant clones are selected by the exposure. However, selective pressures induced by chemotherapy early in life are less well studied. Here, we use single-cell whole genome sequencing and phylogenetic inference to show that the founding cell of t-MN in children starts expanding after cessation of platinum exposure. In patients with Li-Fraumeni syndrome, characterized by a germline TP53 mutation, we find that the t-MN already expands during treatment, suggesting that platinum-induced growth inhibition is TP53-dependent. Our results demonstrate that germline aberrations can interact with treatment exposures in inducing t-MN, which is important for the development of more targeted, patient-specific treatment regimens and follow-up. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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