LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1.
Science
; 302(5644): 415-9, 2003 Oct 17.
Article
em En
| MEDLINE
| ID: mdl-14564000
ABSTRACT
We have previously shown correction of X-linked severe combined immunodeficiency [SCID-X1, also known as gamma chain (gamma(c)) deficiency] in 9 out of 10 patients by retrovirus-mediated gamma(c) gene transfer into autologous CD34 bone marrow cells. However, almost 3 years after gene therapy, uncontrolled exponential clonal proliferation of mature T cells (with gammadelta+ or alphabeta+ T cell receptors) has occurred in the two youngest patients. Both patients' clones showed retrovirus vector integration in proximity to the LMO2 proto-oncogene promoter, leading to aberrant transcription and expression of LMO2. Thus, retrovirus vector insertion can trigger deregulated premalignant cell proliferation with unexpected frequency, most likely driven by retrovirus enhancer activity on the LMO2 gene promoter.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Retroviridae
/
Linfócitos T
/
Terapia Genética
/
Leucemia-Linfoma de Células T do Adulto
/
Imunodeficiência Combinada Severa
/
Proteínas de Ligação a DNA
/
Vetores Genéticos
/
Metaloproteínas
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
/
Infant
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article