Identification of a high incidence region for retroviral vector integration near exon 1 of the LMO2 locus
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Abstract
(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
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- Retrovirology
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Retrovirology 6 2009-09-02
BIOMED CENTRAL LTD
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Details 詳細情報について
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- CRID
- 1050001338914270720
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- NII Article ID
- 120007110393
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- NII Book ID
- AA12051445
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- HANDLE
- 10091/10785
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- ISSN
- 17424690
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- Text Lang
- en
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- Article Type
- journal article
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- Data Source
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- IRDB
- CiNii Articles