Identification of a high incidence region for retroviral vector integration near exon 1 of the <it>LMO2 </it>locus

<p>Abstract</p> <p>Therapeutic retroviral vector integration near the oncogene <it>LMO2 </it>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 <it&g...

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Main Authors: Sakashita Kazuo, Shiozawa Tanri, Osada Ryosuke, Fukushima Yoshimitsu, Wakui Keiko, Kurotori Naoki, Matsuzaki Yasunori, Hatta Mariko, Amano Yuji, Yamashita Yuki, Agawa Hideyuki, Kojima Katsuhiko, Yoshino Kazuhisa, Tsukahara Tomonori, Yamada Koichiro, Koike Kenichi, Kumaki Satoru, Tanaka Nobuyuki, Takeshita Toshikazu
Format: Article
Language:English
Published: BMC 2009-09-01
Series:Retrovirology
Online Access:http://www.retrovirology.com/content/6/1/79
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Summary:<p>Abstract</p> <p>Therapeutic retroviral vector integration near the oncogene <it>LMO2 </it>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 <it>LMO2 </it>locus. We identified a high incidence region (HIR) of vector integration using PCR techniques in the upstream region close to the <it>LMO2 </it>transcription start site in the TPA-Mat T cell line. The integration frequency of the HIR was one per 4.46 × 10<sup>4 </sup>cells. This HIR was also found in Jurkat T cells but was absent from HeLa cells. Furthermore, using human cord blood-derived CD34<sup>+ </sup>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.</p>
ISSN:1742-4690