2024-03-28T19:18:03Z
https://soar-ir.repo.nii.ac.jp/oai
oai:soar-ir.repo.nii.ac.jp:00003917
2022-12-14T04:40:27Z
461:462
Identification of a high incidence region for retroviral vector integration near exon 1 of the LMO2 locus
Yamada, Koichiro
Tsukahara, Tomonori
Yoshino, Kazuhisa
Kojima, Katsuhiko
Agawa, Hideyuki
Yamashita, Yuki
Amano, Yuji
Hatta, Mariko
Matsuzaki, Yasunori
Kurotori, Naoki
Wakui, Keiko
Fukushima, Yoshimitsu
Osada, Ryosuke
Shiozawa, Tanri
Sakashita, Kazuo
Koike, Kenichi
Kumaki, Satoru
Tanaka, Nobuyuki
Takeshita, Toshikazu
(c) 2009 Yamada et al; licensee BioMed Central Ltd. / This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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.
Article
Retrovirology. 6:79 (2009)
journal article
BIOMED CENTRAL LTD
2009-09-02
application/pdf
Retrovirology
6
1742-4690
AA12051445
https://soar-ir.repo.nii.ac.jp/record/3917/files/Identification_high_incidence_region.pdf
eng
19725963
https://pubmed.ncbi.nlm.nih.gov/19725963
10.1186/1742-4690-6-79
https://doi.org/10.1186/1742-4690-6-79