| Autor: |
Daniela Cesana, Maria Pia Cicalese, Andrea Calabria, Pietro Merli, Roberta Caruso, Monica Volpin, Laura Rudilosso, Maddalena Migliavacca, Federica Barzaghi, Claudia Fossati, Francesco Gazzo, Simone Pizzi, Andrea Ciolfi, Alessandro Bruselles, Francesca Tucci, Giulio Spinozzi, Giulia Pais, Fabrizio Benedicenti, Matteo Barcella, Ivan Merelli, Pierangela Gallina, Stefania Giannelli, Francesca Dionisio, Serena Scala, Miriam Casiraghi, Luisa Strocchio, Luciana Vinti, Lucia Pacillo, Eleonora Draghi, Marcella Cesana, Sara Riccardo, Chiara Colantuono, Emmanuelle Six, Marina Cavazzana, Filippo Carlucci, Manfred Schmidt, Caterina Cancrini, Fabio Ciceri, Luca Vago, Davide Cacchiarelli, Bernhard Gentner, Luigi Naldini, Marco Tartaglia, Eugenio Montini, Franco Locatelli, Alessandro Aiuti |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Nature Communications, Vol 15, Iss 1, Pp 1-18 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-024-47866-5 |
| Popis: |
Abstract Hematopoietic stem cell gene therapy (GT) using a γ-retroviral vector (γ-RV) is an effective treatment for Severe Combined Immunodeficiency due to Adenosine Deaminase deficiency. Here, we describe a case of GT-related T-cell acute lymphoblastic leukemia (T-ALL) that developed 4.7 years after treatment. The patient underwent chemotherapy and haploidentical transplantation and is currently in remission. Blast cells contain a single vector insertion activating the LIM-only protein 2 (LMO2) proto-oncogene, confirmed by physical interaction, and low Adenosine Deaminase (ADA) activity resulting from methylation of viral promoter. The insertion is detected years before T-ALL in multiple lineages, suggesting that further hits occurred in a thymic progenitor. Blast cells contain known and novel somatic mutations as well as germline mutations which may have contributed to transformation. Before T-ALL onset, the insertion profile is similar to those of other ADA-deficient patients. The limited incidence of vector-related adverse events in ADA-deficiency compared to other γ-RV GT trials could be explained by differences in transgenes, background disease and patient’s specific factors. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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