ArticleNature communications2024
A case of T-cell acute lymphoblastic leukemia in retroviral gene therapy for ADA-SCID.
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In one paragraph
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
14.3field-weighted citation impact, top 1% of its field
What it found
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Syncytium-forming HSV-1 in cancer gene therapy: From molecular mechanisms to clinical translation.Virulence · 2026Review
- Oncogenesis as an Adverse Effect of Gene Replacement Therapy in Hematopoietic Stem Cells.International journal of molecular sciences · 2026Review
- Spectrum, pathobiology, mechanistic insights and diagnostic challenges of post-CAR T cell therapy lymphoproliferative disorders.Nature reviews. Clinical oncology · 2026Review
- AAV-based gene therapies for neovascular AMD.Gene therapy · 2026Review
- Genetic Findings of Potential Donor Origin in Cells Used for Cell and Gene Therapy: Recommendations from the World Marrow Donor Association.Transplantation and cellular therapy · 2026Review
- RAAVioli: A comprehensive approach to characterizing AAV vector integrations and rearrangements.Molecular therapy. Advances · 2026Article
- Nanoengineered 3D culture substrate enables superior persistence and polyclonal engraftment of genetically engineered hematopoietic stem cells.Cell stem cell · 2026Article
- Gene modification: Exploring the potential in treating kidney diseases.Pharmacological research · 2026Review
- Development of evolutionarily conserved viral integration sites as safe harbors for human gene therapy.iScience · 2025Article
- Ex Vivo Gene and Cell Therapy in Hematopoietic Stem Cells.International journal of molecular sciences · 2025Review
- Gene therapy for inborn errors of immunity: past progress, current status and future directions.Rare disease and orphan drugs journal · 2025Article
- Article
- Preclinical development of lentiviral vector gene therapy for Diamond-Blackfan anemia syndrome.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Clinical hematopoietic stem cell-based gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Current landscape of vector safety and genotoxicity after hematopoietic stem or immune cell gene therapy.Leukemia · 2025Review
- CAR T-cell-associated secondary malignancies challenge current pharmacovigilance concepts.EMBO molecular medicine · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
46 authors at 11 institutions in 3 countries.
Daniela Cesana *San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy.ORCID http://orcid.org/0000-0001-6366-4224
Maria Pia Cicalese *San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy.
Andrea CalabriaSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy.ORCID http://orcid.org/0000-0003-3515-3384
Pietro MerliIRCCS Bambino Gesù Children's Hospital, Rome, Italy.
Roberta CarusoIRCCS Bambino Gesù Children's Hospital, Rome, Italy.
Monica VolpinSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy.ORCID http://orcid.org/0000-0002-0794-9900
Laura RudilossoSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy.
Maddalena MigliavaccaSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy.
Federica BarzaghiSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy.
Claudia FossatiSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy.
Francesco GazzoSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy.
Simone PizziMolecular Genetics and Functional Genomics, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
Andrea CiolfiMolecular Genetics and Functional Genomics, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.ORCID http://orcid.org/0000-0002-6191-0978
Alessandro BrusellesDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
Francesca TucciSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy.
Giulio SpinozziSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy.ORCID http://orcid.org/0000-0002-4220-2474
Giulia PaisSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy.ORCID http://orcid.org/0009-0005-5621-4803
Fabrizio BenedicentiSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy.
Matteo BarcellaSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy.
Ivan MerelliSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy.
Pierangela GallinaSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy.
Stefania GiannelliSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy.
Francesca DionisioSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy.
Serena ScalaSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy.
Miriam CasiraghiSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy.
Luisa StrocchioIRCCS Bambino Gesù Children's Hospital, Rome, Italy.
Luciana VintiIRCCS Bambino Gesù Children's Hospital, Rome, Italy.
Lucia PacilloImmune and Infectious Diseases Division, Research Unit of Primary Immunodeficiencies, Academic Department of Pediatrics, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.ORCID http://orcid.org/0000-0002-7950-8848
Eleonora DraghiImmunogenetics, Leukemia Genomics and Immunobiology Unit, Division of Immunology, Transplantation and Infectious Diseases, Ospedale San Raffaele Scientific Institute, 20132, Milan, Italy.
Marcella CesanaTelethon Institute of Genetics and Medicine (TIGEM), Armenise/Harvard Laboratory of Integrative Genomics, Pozzuoli, Italy.
Sara RiccardoTelethon Institute of Genetics and Medicine (TIGEM), Armenise/Harvard Laboratory of Integrative Genomics, Pozzuoli, Italy.
Chiara ColantuonoTelethon Institute of Genetics and Medicine (TIGEM), Armenise/Harvard Laboratory of Integrative Genomics, Pozzuoli, Italy.ORCID http://orcid.org/0000-0003-3014-6978
Emmanuelle SixLaboratory of Human Lympho-hematopoiesis, INSERM, Paris, France.ORCID http://orcid.org/0000-0001-7806-0968
Marina CavazzanaLaboratory of Human Lympho-hematopoiesis, INSERM, Paris, France.
Filippo CarlucciDepartment of Medical Biotechnologies, University of Siena, Siena, Italy.
Manfred SchmidtGenewerk GmbH, Heidelberg, Germany.
Caterina CancriniImmune and Infectious Diseases Division, Research Unit of Primary Immunodeficiencies, Academic Department of Pediatrics, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
Fabio CiceriSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy.ORCID http://orcid.org/0000-0003-0873-0123
Luca VagoUniversità Vita-Salute San Raffaele, Milan, Italy.ORCID http://orcid.org/0000-0003-4247-3175
Davide CacchiarelliTelethon Institute of Genetics and Medicine (TIGEM), Armenise/Harvard Laboratory of Integrative Genomics, Pozzuoli, Italy.ORCID http://orcid.org/0000-0002-9621-6716
Bernhard GentnerSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy.ORCID http://orcid.org/0000-0001-6024-4718
Luigi NaldiniSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy.ORCID http://orcid.org/0000-0002-7835-527X
Marco TartagliaMolecular Genetics and Functional Genomics, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.ORCID http://orcid.org/0000-0001-7736-9672
Eugenio MontiniSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy.ORCID http://orcid.org/0000-0003-1771-6067
Franco LocatelliDepartment of Pediatric Hematology/Oncology and Cell and Gene Therapy, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.ORCID http://orcid.org/0000-0002-7976-3654
Alessandro AiutiSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy. aiuti.alessandro@hsr.it.ORCID http://orcid.org/0000-0002-5398-1717
The San Raffaele Telethon Institute for Gene Therapy · ITVita-Salute San Raffaele University · ITBambino Gesù Children's Hospital · ITInserm · FRInstitute of Applied Science and Intelligent Systems · ITTelethon Institute Of Genetics And Medicine · ITGene Bridges (Germany) · DEIstituto Superiore di Sanità · ITUniversità Cattolica del Sacro Cuore · ITUniversity of Rome Tor Vergata · ITUniversity of Siena · IT
Funding
Fondazione Italiana per la Ricerca sul Cancro (Italian Foundation for Cancer Research) 9962Fondazione Italiana per la Ricerca sul Cancro (Italian Foundation for Cancer Research) IG #21614Fondazione Italiana per la Ricerca sul Cancro (Italian Foundation for Cancer Research) IG #22197Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research) FOE 2019Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research) PRIN 2017WC8499_004Ministry of Health, Italy | Agenzia Italiana del Farmaco, Ministero della Salute (Italian Medicines Agency) GR-2018-12367860
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.
Indexed as
Adenosine DeaminaseAgammaglobulinemiaGenetic TherapyGenetic VectorsHematopoietic Stem Cell TransplantationPrecursor T-Cell Lymphoblastic Leukemia-LymphomaProto-Oncogene MasSevere Combined ImmunodeficiencyHumansMaleRetroviridaeAdenosine DeaminaseMAS1 protein, humanProto-Oncogene Mas
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.