ArticleLeukemia2008
Leukemia induction after a single retroviral vector insertion in Evi1 or Prdm16.
Article in Leukemia, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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
58 citing papers in PubMed, 94 citations in OpenAlex.
- The oncogenic role of ecotropic viral integration site 1 in hematological malignancies: mechanisms of activation and leukemogenesis.Frontiers in immunology · 2026Review
- Human cancer-targeted immunity via transgenic hematopoietic stem cell progeny.Nature communications · 2025Article
- Expression of a large coding sequence: Gene therapy vectors for Ataxia Telangiectasia.Scientific reports · 2023Article
- EVI1-mediated Programming of Normal and Malignant Hematopoiesis.HemaSphere · 2023Review
- EVI1 expression in early-stage breast cancer patients treated with neoadjuvant chemotherapy.BMC cancer · 2022Article
- BET-Independent Murine Leukemia Virus Integration Is RetargetedMicrobiology spectrum · 2022Article
- Evaluating the state of the science for adeno-associated virus integration: An integrated perspective.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- Improvement of mRNA Delivery Efficiency to a T Cell Line by Modulating PEG-Lipid Content and Phospholipid Components of Lipid Nanoparticles.Pharmaceutics · 2021Article
- Understanding In Vivo Fate of Nucleic Acid and Gene Medicines for the Rational Design of Drugs.Pharmaceutics · 2021Review
- Human Lentiviral Gene Therapy Restores the Cellular Phenotype of Autosomal Recessive Complete IFN-γR1 Deficiency.Molecular therapy. Methods & clinical development · 2020Article
- PRDM16 isoforms differentially regulate normal and leukemic hematopoiesis and inflammatory gene signature.The Journal of clinical investigation · 2018Article
- Preclinical Efficacy and Safety Evaluation of Hematopoietic Stem Cell Gene Therapy in a Mouse Model of MNGIE.Molecular therapy. Methods & clinical development · 2018Article
- Engineering Next-Generation BET-Independent MLV Vectors for Safer Gene Therapy.Molecular therapy. Nucleic acids · 2017Article
- Safe and Effective Gene Therapy for Murine Wiskott-Aldrich Syndrome Using an Insulated Lentiviral Vector.Molecular therapy. Methods & clinical development · 2017Article
- Evaluating the Safety of Retroviral Vectors Based on Insertional Oncogene Activation and Blocked Differentiation in Cultured Thymocytes.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- The interplay of post-translational modification and gene therapy.Drug design, development and therapy · 2016Review
- Improved retroviral episome transfer of transcription factors enables sustained cell fate modification.Gene therapy · 2014Article
- BET-independent MLV-based Vectors Target Away From Promoters and Regulatory Elements.Molecular therapy. Nucleic acids · 2014Article
- Concise review: lessons learned from clinical trials of gene therapy in monogenic immunodeficiency diseases.Stem cells translational medicine · 2014Review
- Pigtailed macaques as a model to study long-term safety of lentivirus vector-mediated gene therapy for hemoglobinopathies.Molecular therapy. Methods & clinical development · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 2 countries.
Funding
Abstract
Insertional activation of cellular proto-oncogenes by replication-defective retroviral vectors can trigger clonal dominance and leukemogenesis in animal models and clinical trials. Here, we addressed the leukemogenic potential of vectors expressing interleukin-2 receptor common gamma-chain (IL2RG), the coding sequence required for correction of X-linked severe combined immunodeficiency. Similar to conventional gamma-retroviral vectors, self-inactivating (SIN) vectors with strong internal enhancers also triggered profound clonal imbalance, yet with a characteristic insertion preference for a window located downstream of the transcriptional start site. Controls including lentivirally transduced cells revealed that ectopic IL2RG expression was not sufficient to trigger leukemia. After serial bone marrow transplantation involving 106 C57Bl6/J mice monitored for up to 18 months, we observed leukemic progression of six distinct clones harboring gamma-retroviral long terminal repeat (LTR) or SIN vector insertions in Evi1 or Prdm16, two functionally related genes. Three leukemic clones had single vector integrations, and identical clones manifested with a remarkably similar latency and phenotype in independent recipients. We conclude that upregulation of Evi1 or Prdm16 was sufficient to initiate a leukemogenic cascade with consistent intrinsic dynamics. Our study also shows that insertional mutagenesis is required for leukemia induction by IL2RG vectors, a risk to be addressed by improved vector design.
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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.