Trial reportThe Journal of clinical investigation2008
Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1.
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. Cited by 945 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
945 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,810 citations in OpenAlex.
- A Systematic Review of Clinical Trials Using mRNA Vaccines for Infectious Diseases other than COVID-19.British journal of biomedical science · 2025Pooled it
- A systematic review and meta-analysis of gene therapy with hematopoietic stem and progenitor cells for monogenic disorders.Nature communications · 2022Pooled it
- 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
- Gene therapy for hereditary hematological disorders: From clinical breakthroughs to future horizons.Molecular therapy. Nucleic acids · 2026Review
- Engineering hematopoietic stem and progenitor cells to generate red blood cells as viral traps against HIV-1.Molecular therapy. Advances · 2026Article
- A review of genetic modification for ex vivo cellular therapies.Transfusion · 2026Article
- Review
- Oncogenesis as an Adverse Effect of Gene Replacement Therapy in Hematopoietic Stem Cells.International journal of molecular sciences · 2026Review
- Engineered iMSCs delivering wild-type IL-2 achieve dose-sparing tumor control via CD25-dependent CD8BMC medicine · 2026Article
- Modeling and correction of SCID-X1 using CRISPR-Cas9 homology-directed repair in human HSPCs.Molecular therapy. Nucleic acids · 2026Article
- Targeting GD2 with CAR-T Cell Therapy in Neuroblastoma: Updates, Challenges, and Future Perspectives.Current oncology reports · 2026Review
- A Comprehensive Evaluation of CAR-T Cell Gene Therapy, Tracing its Revolutionary Clinical Breakthroughs and Advancements Towards Next-Generation Engineering.Expert reviews in molecular medicine · 2026Review
- Review
- In vivo CAR-cell therapy: current challenges and emerging therapeutic advances.Molecular biomedicine · 2026Review
- Gene Therapy-Related Malignancy and the Risk of Cancer Exceptionalism.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2026Article
- CAR-NK cell therapy for hematologic malignancies: advances, challenges and optimization strategies.Molecular cancer · 2026Review
- Gene modification: Exploring the potential in treating kidney diseases.Pharmacological research · 2026Review
- In vivo engineering of CAR-T cells: delivery strategies and clinical translation.Biomarker research · 2026Review
- Unleashing CAR-T potential in solid tumors: overcoming intrinsic and extrinsic hurdles to improve therapy.Cancer immunology, immunotherapy : CII · 2026Review
885 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
29 authors at 9 institutions in 4 countries.
Funding
Abstract
Previously, several individuals with X-linked SCID (SCID-X1) were treated by gene therapy to restore the missing IL-2 receptor gamma (IL2RG) gene to CD34+ BM precursor cells using gammaretroviral vectors. While 9 of 10 patients were successfully treated, 4 of the 9 developed T cell leukemia 31-68 months after gene therapy. In 2 of these cases, blast cells contained activating vector insertions near the LIM domain-only 2 (LMO2) proto-oncogene. Here, we report data on the 2 most recent adverse events, which occurred in patients 7 and 10. In patient 10, blast cells contained an integrated vector near LMO2 and a second integrated vector near the proto-oncogene BMI1. In patient 7, blast cells contained an integrated vector near a third proto-oncogene,CCND2. Additional genetic abnormalities in the patients' blast cells included chromosomal translocations, gain-of-function mutations activating NOTCH1, and copy number changes, including deletion of tumor suppressor gene CDKN2A, 6q interstitial losses, and SIL-TAL1 rearrangement. These findings functionally specify a genetic network that controls growth in T cell progenitors. Chemotherapy led to sustained remission in 3 of the 4 cases of T cell leukemia, but failed in the fourth. Successful chemotherapy was associated with restoration of polyclonal transduced T cell populations. As a result, the treated patients continued to benefit from therapeutic gene transfer.
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.