ArticleNature medicine2023
Clonal selection of hematopoietic stem cells after gene therapy for sickle cell disease.
Article in Nature medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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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.
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Who cites it
37 citing papers in PubMed, 47 citations in OpenAlex.
- Lentiviral gene therapy with reduced-intensity conditioning for sickle cell disease: a phase 1/2 trial.Nature medicine · 2025Trial
- Severe inflammation and lineage skewing are associated with poor engraftment of engineered hematopoietic stem cells in patients with sickle cell disease.Nature communications · 2025Trial
- Systemic delivery of phagocytosis-shielded retroviral vectors enables in vivo HSC gene therapy for sickle cell disease.Cell stem cell · 2026Article
- Single-cell vector copy number analysis of phenotypically defined long-term hematopoietic stem cells for gene therapy safety assessment.Molecular therapy. Advances · 2026Article
- The Evolution of Polyclonal Competition in Aging Hematopoiesis.Cancer discovery · 2026Article
- Premature senescence impairs hematopoietic stem cell function during sickle cell disease in mice and humans.Science translational medicine · 2026Article
- Clonal hematopoiesis in the setting of sickle cell disease and its relevance to curative therapies.Seminars in hematology · 2026Article
- Should Sickle Cell Disease Be Considered a Cancer Predisposition Syndrome?Children (Basel, Switzerland) · 2026Review
- CRISPR-Cas9 Therapeutics in Early Clinical Development: Delivery and Molecular Diagnostics.Cells · 2026Review
- Molecular Testing in Sickle Cell Disease: From Newborn Screening to Transfusion Care.International journal of laboratory hematology · 2026Review
- The Molecular Pathology of Non-Malignant Haematological Disease.British journal of biomedical science · 2026Review
- In situ gene editing of hematopoietic stem cells via AAV-delivered CRISPR guide RNAs.Blood advances · 2025Article
- Development of evolutionarily conserved viral integration sites as safe harbors for human gene therapy.iScience · 2025Article
- Gene therapy for hemoglobinopathies: Clinical trial results and biology of hematopoietic stem cell and the bone marrow niche.Cell reports. Medicine · 2025Review
- Gene Therapy of Beta Hemoglobinopathies.Biomedicines · 2025Review
- Posttransplantation clonal dynamics of hematopoietic stem cells carrying prenatal and early-lifeHemaSphere · 2025Article
- Article
- When Blood Disorders Meet Cancer: Uncovering the Oncogenic Landscape of Sickle Cell Disease.Journal of clinical medicine · 2025Review
- Cyp7b1-inhibiting azoles as novel enhancers of hematopoietic stem and progenitor cell mobilization.bioRxiv : the preprint server for biology · 2025Article
- Segregating DNA lesions point to high selective advantage of tumor initiating cells.bioRxiv : the preprint server for biology · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 8 institutions in 3 countries.
Funding
Abstract
Gene therapy (GT) provides a potentially curative treatment option for patients with sickle cell disease (SCD); however, the occurrence of myeloid malignancies in GT clinical trials has prompted concern, with several postulated mechanisms. Here, we used whole-genome sequencing to track hematopoietic stem cells (HSCs) from six patients with SCD at pre- and post-GT time points to map the somatic mutation and clonal landscape of gene-modified and unmodified HSCs. Pre-GT, phylogenetic trees were highly polyclonal and mutation burdens per cell were elevated in some, but not all, patients. Post-GT, no clonal expansions were identified among gene-modified or unmodified cells; however, an increased frequency of potential driver mutations associated with myeloid neoplasms or clonal hematopoiesis (DNMT3A- and EZH2-mutated clones in particular) was observed in both genetically modified and unmodified cells, suggesting positive selection of mutant clones during GT. This work sheds light on HSC clonal dynamics and the mutational landscape after GT in SCD, highlighting the enhanced fitness of some HSCs harboring pre-existing driver mutations. Future studies should define the long-term fate of mutant clones, including any contribution to expansions associated with myeloid neoplasms.
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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.