ArticleThe Journal of clinical investigation2008
High incidence of leukemia in large animals after stem cell gene therapy with a HOXB4-expressing retroviral vector.
Article 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 64 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
64 citing papers in PubMed, 107 citations in OpenAlex.
- Applications of Innovation Technologies for Personalized Cancer Medicine: Stem Cells and Gene-Editing Tools.ACS pharmacology & translational science · 2023Review
- L-Cells · 2021Article
- Cell and Gene Therapy for Anemia: Hematopoietic Stem Cells and Gene Editing.International journal of molecular sciences · 2021Review
- A novel DNA methylation-based model that effectively predicts prognosis in hepatocellular carcinoma.Bioscience reports · 2021Article
- Comparative engraftment and clonality of macaque HSPCs expanded on human umbilical vein endothelial cells versus non-expanded cells.Molecular therapy. Methods & clinical development · 2021Article
- Developments and translational relevance for the canine haematopoietic cell transplantation preclinical model.Veterinary and comparative oncology · 2020Review
- RNA-binding protein IGF2BP1 maintains leukemia stem cell properties by regulating HOXB4, MYB, and ALDH1A1.Leukemia · 2020Article
- The Actin Binding Protein Plastin-3 Is Involved in the Pathogenesis of Acute Myeloid Leukemia.Cancers · 2019Article
- Barcoding of Macaque Hematopoietic Stem and Progenitor Cells: A Robust Platform to Assess Vector Genotoxicity.Molecular therapy. Methods & clinical development · 2018Article
- In vivo selection with lentiviral expression of Bcl2Gene therapy · 2018Article
- Enhancement of mouse hematopoietic stem/progenitor cell function via transient gene delivery using integration-deficient lentiviral vectors.Experimental hematology · 2018Article
- Human mesenchymal stromal cells as cellular drug-delivery vectors for glioblastoma therapy: a good deal?Journal of experimental & clinical cancer research : CR · 2017Article
- Seeking the "mother of blood" from human pluripotent stem cells: Are we there yet?Genes & diseases · 2017Article
- Hit-and-run programming of therapeutic cytoreagents using mRNA nanocarriers.Nature communications · 2017Article
- [Generation of engraftable hematopoietic stem cells from human pluripotent stem cells].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2017Article
- Use of genome-editing tools to treat sickle cell disease.Human genetics · 2016Review
- Insulators to Improve the Safety of Retroviral Vectors for HIV Gene Therapy.Biomedicines · 2016Article
- GSK3β Inhibition Promotes Efficient Myeloid and Lymphoid Hematopoiesis from Non-human Primate-Induced Pluripotent Stem Cells.Stem cell reports · 2016Article
- Mesenchymal stromal cells loaded with paclitaxel induce cytotoxic damage in glioblastoma brain xenografts.Stem cell research & therapy · 2015Article
- Human amniotic mesenchymal stromal cells (hAMSCs) as potential vehicles for drug delivery in cancer therapy: an in vitro study.Stem cell research & therapy · 2015Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
Retroviral vector-mediated HSC gene therapy has been used to treat individuals with a number of life-threatening diseases. However, some patients with SCID-X1 developed retroviral vector-mediated leukemia after treatment. The selective growth advantage of gene-modified cells in patients with SCID-X1 suggests that the transgene may have played a role in leukemogenesis. Here we report that 2 of 2 dogs and 1 of 2 macaques developed myeloid leukemia approximately 2 years after being transplanted with cells that overexpressed homeobox B4 (HOXB4) and cells transduced with a control gammaretroviral vector that did not express HOXB4. The leukemic cells had dysregulated expression of oncogenes, a block in myeloid differentiation, and overexpression of HOXB4. HOXB4 knockdown restored differentiation in leukemic cells, suggesting involvement of HOXB4. In contrast, leukemia did not arise from the cells carrying the control gammaretroviral vector. In addition, leukemia did not arise in 5 animals with high-level marking and polyclonal long-term repopulation following transplantation with cells transduced with an identical gammaretrovirus vector backbone expressing methylguanine methyltransferase. These findings, combined with the absence of leukemia in many other large animals transplanted with cells transduced with gammaretroviral vectors expressing genes other than HOXB4, show that HOXB4 overexpression poses a significant risk of leukemogenesis. Our data thus suggest the continued need for caution in genetic manipulation of repopulating cells, particularly when the transgene might impart an intrinsic growth advantage.
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.