Identification of a high incidence region for retroviral vector integration near exon 1 of the LMO2 locus.
Retrovirology
; 6: 79, 2009 Sep 02.
Article
in En
| MEDLINE
| ID: mdl-19725963
ABSTRACT
Therapeutic retroviral vector integration near the oncogene LMO2 is thought to be a cause of leukemia in X-SCID gene therapy trials. However, no published studies have evaluated the frequency of vector integrations near exon 1 of the LMO2 locus. We identified a high incidence region (HIR) of vector integration using PCR techniques in the upstream region close to the LMO2 transcription start site in the TPA-Mat T cell line. The integration frequency of the HIR was one per 4.46 x 10(4) cells. This HIR was also found in Jurkat T cells but was absent from HeLa cells. Furthermore, using human cord blood-derived CD34+ cells we identified a HIR in a similar region as the TPA-Mat T cell line. One of the X-linked severe combined immunodeficiency (X-SCID) patients that developed leukemia after gene therapy had a vector integration site in this HIR. Therefore, the descriptions of the location and the integration frequency of the HIR presented here may help us to better understand vector-induced leukemogenesis.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Retroviridae
/
T-Lymphocytes
/
Genetic Therapy
/
Exons
/
Virus Integration
/
DNA-Binding Proteins
/
Genetic Vectors
/
Metalloproteins
Type of study:
Diagnostic_studies
/
Incidence_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Retrovirology
Journal subject:
VIROLOGIA
Year:
2009
Type:
Article
Affiliation country:
Japan