Title |
Identification of a high incidence region for retroviral vector integration near exon 1 of the LMO2locus
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Published in |
Retrovirology, September 2009
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DOI | 10.1186/1742-4690-6-79 |
Pubmed ID | |
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. |
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