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
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...
April 30, 2024: Nature Communications