ReviewGene therapy2008
Insertional mutagenesis and clonal dominance: biological and statistical considerations.
Review in Gene therapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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
28 citing papers in PubMed.
- Efficient in vivo targeting of the myocardial scar using Moloney murine leukaemia virus complexed with nanoparticles.The Journal of physiology · 2026Article
- Modeling integration site data for safety assessment with MELISSA.Nature communications · 2025Article
- Gene Therapy: An Historical Overview for Familial Hearing Loss.International journal of molecular sciences · 2025Review
- Gene Therapy in Orthopaedics: Progress and Challenges in Pre-Clinical Development and Translation.Frontiers in bioengineering and biotechnology · 2022Review
- Functional compensation between hematopoietic stem cell clonesEMBO reports · 2018Article
- Transplantation Dose Alters the Differentiation Program of Hematopoietic Stem Cells.Cell reports · 2016Article
- Gene Therapy for X-Linked Severe Combined Immunodeficiency: Where Do We Stand?Human gene therapy · 2016Review
- A comparison of foamy and lentiviral vector genotoxicity in SCID-repopulating cells shows foamy vectors are less prone to clonal dominance.Molecular therapy. Methods & clinical development · 2016Article
- Coherence analysis discriminates between retroviral integration patterns in CD34(+) cells transduced under differing clinical trial conditions.Molecular therapy. Methods & clinical development · 2015Article
- Postzygotic single-nucleotide mosaicisms in whole-genome sequences of clinically unremarkable individuals.Cell research · 2014Article
- Transcription activator like effector (TALE)-directed piggyBac transposition in human cells.Nucleic acids research · 2013Article
- Mathematical modeling of oncogenesis control in mature T-cell populations.Frontiers in immunology · 2013Article
- Development of the Nanobody display technology to target lentiviral vectors to antigen-presenting cells.Gene therapy · 2012Article
- Chimeric piggyBac transposases for genomic targeting in human cells.Nucleic acids research · 2012Article
- Gene and cell therapy based treatment strategies for inflammatory bowel diseases.World journal of gastrointestinal pathophysiology · 2011Article
- Insertion sites in engrafted cells cluster within a limited repertoire of genomic areas after gammaretroviral vector gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2011Article
- Efficacy and safety of Sleeping Beauty transposon-mediated gene transfer in preclinical animal studies.Current gene therapy · 2011Review
- Gene therapy strategies: can we eradicate HIV?Current HIV/AIDS reports · 2011Article
- Duration of expression and activity of Sleeping Beauty transposase in mouse liver following hydrodynamic DNA delivery.Molecular therapy : the journal of the American Society of Gene Therapy · 2010Article
- Signed outside: a surface marker system for transgenic cytoplasmic proteins.Gene therapy · 2010Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Improvements of (retroviral) gene transfer vectors, stem cell isolation and culture techniques as well as transduction protocols eventually resulted not only in the successful genetic modification of cells capable of reconstituting the haematopoietic system in various animal models, but also human beings. This was a conditio sine qua non for the successful application of gene therapy for inherited diseases as meanwhile achieved for severe combined immune deficiencies (SCID-X1, ADA-SCID) and chronic granulomatous disease (CGD). Unexpectedly, in long-term animal experiments as well as in the follow up of patients from the CGD trial, haematopoietic clones bearing insertions in certain gene loci became dominant, which was most apparent in the myeloid blood compartment. Accumulating data strongly suggest that this clonal dominance was due to some growth and/or survival advantage conferred by gene-activating or -suppressing effects of the integrated retroviral vector (insertional mutagenesis). Importantly, such induced clonal dominance seems not to lead to malignant transformation of affected cell clones inadvertently. The latter finding has become the basis for the concept of 'induced haematopoietic stem cells', a potentially powerful tool to investigate genes involved in the regulation of mechanisms underlying competitive advantages of stem cells, but also in the multi-step nature of malignant transformation. Here we discuss promises and open issues of this concept as well as the important question of common insertion sites statistics and its pitfalls.
Indexed as
Identifiers
17972922What 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.