High-definition mapping of retroviral integration sites defines the fate of allogeneic T cells after donor lymphocyte infusion.

ABSTRACT: The infusion of donor lymphocytes transduced with a retroviral vector expressing the HSV-TK suicide gene in patients undergoing hematopoietic stem cell transplantation for leukemia/lymphoma promotes immune reconstitution and prevents infections and graft-versus-host disease. Analysis of the clonal dynamics of genetically modified lymphocytes in vivo is of crucial importance to understand the potential genotoxic risk of this therapeutic approach. We used linear amplification-mediated PCR and pyrosequencing to build a genome-wide, high-definition map of retroviral integration sites in the genome of peripheral blood T cells from two different donors and used gene expression profiling and bioinformatics to associate integration clusters to transcriptional activity and to genetic and epigenetic

SUBMITTER: Cattoglio C 

PROVIDER: S-EPMC3008730 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature