title: Long-term vector integration site analysis following retroviral mediated gene transfer to hematopoietic stem cells for the treatment of HIV infection.
abstract: We previously reported the efficacy of nonmyeloablative allogeneic transplantation in 2 HIV positive recipients, one of whom received retrovirus transduced hematopoietic stem cells to confer resistance to HIV. Here we report an assessment of retroviral integration sites (RISs) recovered out to 3 years post-transplantation. We identified 213 unique RISs from the patient's peripheral blood samples by linear amplification-mediated PCR (LAM-PCR). While vector integration patterns were similar to that previously reported, only 3.76% of RISs were common among early (up to 3 months) and late samples (beyond 1 year). Additionally, common integration sites were enriched among late samples (14.9% vs. 36.8%, respectively). Three RISs were found near or within known oncogenes, but 2 were limited to early timepoints. Interestingly, an integration site near the MDS1 gene was detected in long-term follow-up samples; however, the overall contribution of MDS1 integrated clone remained stably low during follow-up.
authors.affiliation: National Institutes of Diabetes and Digestive and Kidney Disorders (NIDDK) and National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, Maryland, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Hayakawa
authors.forename: Kareem
authors.initials: K
authors.lastname: Washington
authors.forename: Naoya
authors.initials: N
authors.lastname: Uchida
authors.forename: Oswald
authors.initials: O
authors.lastname: Phang
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Kang
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Hsieh
authors.forename: John F
authors.initials: JF
authors.lastname: Tisdale
mesh_terms: D004268:DNA-Binding Proteins; D018390:Gene Targeting; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D015658:HIV Infections / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells; D006801:Humans; D000074008:MDS1 and EVI1 Complex Locus Protein; D009363:Neoplasm Proteins / Q000235:genetics; D011519:Proto-Oncogenes; D012190:Retroviridae / Q000235:genetics; D014157:Transcription Factors; D014161:Transduction, Genetic; D016662:Virus Integration
chemical_list: D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; D009363:Neoplasm Proteins; D014157:Transcription Factors