Abstract
Emerging evidence indicates that thymocyte self-renewal induced by progenitor deprivation carries an oncogenic risk that is modulated by intra-thymic competition from differentiation-committed cells. Here we discuss formative studies demonstrating that, in mice, early thymocytes acquire self-renewing potential when thymic progenitor supply is sub-physiological and the importance of cellular competition with this at-risk cell population to prevent lymphoid malignancy. We also consider the possibility that increased thymic residency time, established under conditions of limited cellular competition, may have contributed to oncogenesis observed in early SCID-X1 trials when combined with insertional activation of proto-oncogenes such as LMO2.
| Original language | English |
|---|---|
| Pages (from-to) | 771-776 |
| Number of pages | 6 |
| Journal | Mammalian Genome |
| Volume | 29 |
| Issue number | 11-12 |
| DOIs | |
| Publication status | Published - 1 Dec 2018 |
Cite this
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Thymocyte self-renewal and oncogenic risk in immunodeficient mouse models : relevance for human gene therapy clinical trials targeting haematopoietic stem cell populations? / Ginn, Samantha L.; McCormack, Matthew P.; Alexander, Ian E.
In: Mammalian Genome, Vol. 29, No. 11-12, 01.12.2018, p. 771-776.Research output: Contribution to journal › Review Article › Research › peer-review
TY - JOUR
T1 - Thymocyte self-renewal and oncogenic risk in immunodeficient mouse models
T2 - relevance for human gene therapy clinical trials targeting haematopoietic stem cell populations?
AU - Ginn, Samantha L.
AU - McCormack, Matthew P.
AU - Alexander, Ian E.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Emerging evidence indicates that thymocyte self-renewal induced by progenitor deprivation carries an oncogenic risk that is modulated by intra-thymic competition from differentiation-committed cells. Here we discuss formative studies demonstrating that, in mice, early thymocytes acquire self-renewing potential when thymic progenitor supply is sub-physiological and the importance of cellular competition with this at-risk cell population to prevent lymphoid malignancy. We also consider the possibility that increased thymic residency time, established under conditions of limited cellular competition, may have contributed to oncogenesis observed in early SCID-X1 trials when combined with insertional activation of proto-oncogenes such as LMO2.
AB - Emerging evidence indicates that thymocyte self-renewal induced by progenitor deprivation carries an oncogenic risk that is modulated by intra-thymic competition from differentiation-committed cells. Here we discuss formative studies demonstrating that, in mice, early thymocytes acquire self-renewing potential when thymic progenitor supply is sub-physiological and the importance of cellular competition with this at-risk cell population to prevent lymphoid malignancy. We also consider the possibility that increased thymic residency time, established under conditions of limited cellular competition, may have contributed to oncogenesis observed in early SCID-X1 trials when combined with insertional activation of proto-oncogenes such as LMO2.
UR - http://www.scopus.com/inward/record.url?scp=85052939695&partnerID=8YFLogxK
U2 - 10.1007/s00335-018-9780-5
DO - 10.1007/s00335-018-9780-5
M3 - Review Article
AN - SCOPUS:85052939695
VL - 29
SP - 771
EP - 776
JO - Mammalian Genome
JF - Mammalian Genome
SN - 0938-8990
IS - 11-12
ER -