Trial reportThe Journal of clinical investigation2008
Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients.
Trial report in The Journal of clinical investigation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 661 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Lentiviral Gene Transfer for Treatment of Children Older Than 2 Years of Age With X-Linked Severe Combined Immunodeficiency
Phase I/II Safety and Efficacy Study of Gene Transfer for Artemis-Deficient Severe Combined Immunodeficiency (ART-SCID) in Newly Diagnosed Patients Using Self-Inactivating Lentiviral Vector (AProArt) to Transduce Autologous CD34 Hematopoietic Cells
Who cites it
661 citing papers in PubMed, 1,267 citations in OpenAlex.
- Outcomes following treatment for ADA-deficient severe combined immunodeficiency: a report from the PIDTC.Blood · 2022Trial
- Lentivector cryptic splicing mediates increase in CD34+ clones expressing truncated HMGA2 in human X-linked severe combined immunodeficiency.Nature communications · 2022Trial
- Long-term outcomes after gene therapy for adenosine deaminase severe combined immune deficiency.Blood · 2021Trial
- Autologous Ex Vivo Lentiviral Gene Therapy for Adenosine Deaminase Deficiency.The New England journal of medicine · 2021Trial
- From Delivery to Design: Site-Specific Genome Engineering for Next-Generation CAR T-Cell Therapy.Biomedicines · 2026Review
- RNA delivery to the corneal endothelium using charge-altering releasable transporters.Science advances · 2026Article
- Evolution of Inborn Errors of Immunity in China: Discoveries and Treatment Paradigms.Clinical reviews in allergy & immunology · 2026Review
- Modeling and correction of SCID-X1 using CRISPR-Cas9 homology-directed repair in human HSPCs.Molecular therapy. Nucleic acids · 2026Article
- intmap: fast and flexible mapping of mobile DNA integration for basic and translational research.Bioinformatics (Oxford, England) · 2026Article
- Editors' Note: Gene Therapy and Rare Diseases Through the Ages: Stories of Science and Society.The Yale journal of biology and medicine · 2026Article
- CRISPR-Cas9 engineering of CAR-T cells: Can non-viral nanoparticles unlock safer and scalable genome editing?iScience · 2026Review
- Advancements in Gene Delivery using Nucleic Acid Loaded Nanoparticles for Region Specific Delivery in Alzheimer's Disease.Molecular neurobiology · 2026Review
- A Novel Strategy to Produce CAR-γδ T Cells via Site-Directed Gene Integration by a Combination of CRISPR/Cas9 and AAV.Cancer medicine · 2026Article
- mRNA Lipid Nanoparticles for Cell Engineering in Vivo and in Vitro: Current Applications and Future Directions.MedComm · 2026Review
- Targeting Neurovascular Pathways: Gene Therapy as a Novel Treatment for Vascular Dementia After Stroke.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2026Review
- Application Advances of Lentiviral Vectors: From Gene Therapy to Vaccine Development.Molecular biotechnology · 2026Review
- 7SK-enriched exosomes suppress the cancer phenotypes in human lung cancer cells: insights from 2D and microfluidic 3D in vitro models.Scientific reports · 2026Article
- Position statement from the British Society of Blood and Marrow Transplantation and Cellular Therapy on insertional oncogenesis in gene-engineered advanced cell therapy products for treatment of haematological disorders.British journal of haematology · 2026Article
- Gene modification: Exploring the potential in treating kidney diseases.Pharmacological research · 2026Review
- Adaptation of lentiviral vectors for viral gene therapy and their impact on host cell biology.Journal of translational medicine · 2026Review
601 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
27 authors at 7 institutions in 6 countries.
Funding
Abstract
X-linked SCID (SCID-X1) is amenable to correction by gene therapy using conventional gammaretroviral vectors. Here, we describe the occurrence of clonal T cell acute lymphoblastic leukemia (T-ALL) promoted by insertional mutagenesis in a completed gene therapy trial of 10 SCID-X1 patients. Integration of the vector in an antisense orientation 35 kb upstream of the protooncogene LIM domain only 2 (LMO2) caused overexpression of LMO2 in the leukemic clone. However, leukemogenesis was likely precipitated by the acquisition of other genetic abnormalities unrelated to vector insertion, including a gain-of-function mutation in NOTCH1, deletion of the tumor suppressor gene locus cyclin-dependent kinase 2A (CDKN2A), and translocation of the TCR-beta region to the STIL-TAL1 locus. These findings highlight a general toxicity of endogenous gammaretroviral enhancer elements and also identify a combinatorial process during leukemic evolution that will be important for risk stratification and for future protocol design.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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 OpenQuestion graph.