Evidence map›Paper›PMID 28325276›Full record

ArticleMolecular therapy. Nucleic acids2017

Limiting Thymic Precursor Supply Increases the Risk of Lymphoid Malignancy in Murine X-Linked Severe Combined Immunodeficiency.

Samantha L Ginn, Claus V Hallwirth, Sophia H Y Liao, Erdahl T Teber, Jonathan W Arthur, Jianmin Wu, Hong Ching Lee, Szun S Tay, Min Hu, Roger R Reddel and 5 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy. Nucleic acids, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
3.3field-weighted citation impact, top 8% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Review
  10. Nuclease-free Adeno-Associated Virus-Mediated Il2rg Gene Editing in X-SCID Mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2018
    Article
  11. Evolving Gene Therapy in Primary Immunodeficiency.Molecular therapy : the journal of the American Society of Gene Therapy · 2017
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 9 institutions in 3 countries.

Samantha L GinnGene Therapy Research Unit, Children's Medical Research Institute, The University of Sydney and The Sydney Children's Hospitals Network, Westmead, NSW 2145, Australia.
Claus V HallwirthGene Therapy Research Unit, Children's Medical Research Institute, The University of Sydney and The Sydney Children's Hospitals Network, Westmead, NSW 2145, Australia.
Sophia H Y LiaoGene Therapy Research Unit, Children's Medical Research Institute, The University of Sydney and The Sydney Children's Hospitals Network, Westmead, NSW 2145, Australia.
Erdahl T TeberBioinformatics Unit, Children's Medical Research Institute, The University of Sydney, Westmead, NSW 2145, Australia.
Jonathan W ArthurBioinformatics Unit, Children's Medical Research Institute, The University of Sydney, Westmead, NSW 2145, Australia.
Jianmin WuKinghorn Cancer Centre & Cancer Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, University of New South Wales, Darlinghurst, NSW 2010, Australia.
Hong Ching LeeKinghorn Cancer Centre & Cancer Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, University of New South Wales, Darlinghurst, NSW 2010, Australia.
Szun S TayGene Therapy Research Unit, Children's Medical Research Institute, The University of Sydney and The Sydney Children's Hospitals Network, Westmead, NSW 2145, Australia.
Min HuCentre for Kidney Research of The Children's Hospital at Westmead, Westmead, NSW 2145, Australia.
Roger R ReddelCancer Research Unit, Children's Medical Research Institute, The University of Sydney, Westmead, NSW 2145, Australia.
Matthew P McCormackAustralian Centre for Blood Diseases, Monash University, Melbourne, VIC 3800, Australia.
Adrian J ThrasherInfection, Immunity, Inflammation, UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK.
Marina CavazzanaDepartment of Biotherapy, Hôpital Necker-Enfants Malades, Paris 75015, France.
Stephen I AlexanderCentre for Kidney Research of The Children's Hospital at Westmead, Westmead, NSW 2145, Australia; Discipline of Child and Adolescent Health, The University of Sydney, Westmead, NSW 2145, Australia.
Ian E AlexanderGene Therapy Research Unit, Children's Medical Research Institute, The University of Sydney and The Sydney Children's Hospitals Network, Westmead, NSW 2145, Australia; Discipline of Child and Adolescent Health, The University of Sydney, Westmead, NSW 2145, Australia. Electronic address: ian.alexander@health.nsw.gov.au.
Children's Medical Research Institute · AUUniversity of Sydney · AUChildren's Hospital at Westmead · AUSydney Children’s Hospitals Network · AUGarvan Institute of Medical Research · AUHôpital Necker-Enfants Malades · FRMonash University · AUUniversity College London · GBUNSW Sydney · AU

Funding

Wellcome Trust
6 · The paper itself

Abstract

In early gene therapy trials for SCID-X1, using γ-retroviral vectors, T cell leukemias developed in a subset of patients secondary to insertional proto-oncogene activation. In contrast, we have reported development of T cell leukemias in SCID-X1 mice following lentivirus-mediated gene therapy independent of insertional mutagenesis. A distinguishing feature in our study was that only a proportion of transplanted γc-deficient progenitors were transduced and therefore competent for reconstitution. We hypothesized that reconstitution of SCID-X1 mice with limiting numbers of hematopoietic progenitors might be a risk factor for lymphoid malignancy. To test this hypothesis, in the absence of transduction, SCID-X1 mice were reconstituted with serially fewer wild-type hematopoietic progenitors. A robust inverse correlation between hematopoietic progenitor cell dose and T-lymphoid malignancy was observed, with earlier disease onset at lower cell doses. Malignancies were of donor origin and carried activating Notch1 mutations. These findings align with emerging evidence that thymocyte self-renewal induced by progenitor deprivation carries an oncogenic risk that is modulated by intra-thymic competition from differentiation-committed cells. Although insertional proto-oncogene activation is required for the development of malignancy in humans, failure of γc-deficient thymocytes to effectively compete with this at-risk cell population may have also contributed to oncogenesis observed in early SCID-X1 trials.

Indexed as

gene therapylymphomagenesisprimary immune deficiencySCID-X1self-renewalthymus

Identifiers

PMID28325276
PMCPMC5363493
OpenAlexW2563718832

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.