Retrovirology (Sep 2009)

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

  • 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

DOI
https://doi.org/10.1186/1742-4690-6-79
Journal volume & issue
Vol. 6, no. 1
p. 79

Abstract

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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 × 104 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.