Identification of a high incidence region for retroviral vector integration near exon 1 of the LMO2locus View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2009-12

AUTHORS

Koichiro Yamada, Tomonori Tsukahara, Kazuhisa Yoshino, Katsuhiko Kojima, Hideyuki Agawa, Yuki Yamashita, Yuji Amano, Mariko Hatta, Yasunori Matsuzaki, Naoki Kurotori, Keiko Wakui, Yoshimitsu Fukushima, Ryosuke Osada, Tanri Shiozawa, Kazuo Sakashita, Kenichi Koike, Satoru Kumaki, Nobuyuki Tanaka, Toshikazu Takeshita

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. More... »

PAGES

79

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/1742-4690-6-79

DOI

http://dx.doi.org/10.1186/1742-4690-6-79

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1016034898

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19725963


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Download the RDF metadata as:  json-ld nt turtle xml License info

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RDF/XML is a standard XML format for linked data.

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