Thymocyte self-renewal and oncogenic risk in immunodeficient mouse models: relevance for human gene therapy clinical trials targeting haematopoietic stem cell populations?
Mamm Genome
; 29(11-12): 771-776, 2018 12.
Article
en En
| MEDLINE
| ID: mdl-30182300
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Proteínas Adaptadoras Transductoras de Señales
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Timocitos
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Proteínas con Dominio LIM
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Carcinogénesis
/
Neoplasias
Tipo de estudio:
Etiology_studies
/
Risk_factors_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Mamm Genome
Asunto de la revista:
GENETICA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Australia