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>
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