A retroviral vector common integration site between leupaxin and zinc finger protein 91 ( ZFP91) observed in baboon hematopoietic repopulating cells

Abstract

Retroviral vector proviruses can lead to aberrant expression of nearby genes in hematopoietic repopulating cells, leading to an over-representation of clones with dysregulated genes that affect hematopoiesis. Common integration sites (CISs) identified using the vector provirus as a molecular tag can be used to identify these genes. Here we characterized a retroviral CIS observed at high frequency in baboon hematopoietic repopulating cells that has not been described previously. Gammaretroviral vector integration sites in baboon repopulating cells identified by polymerase chain reaction amplification were localized to the human genome to identify a CIS. The presence of each clone was tracked over time using allele-specific polymerase chain reaction. In three different animals that received gammaretrovirally transduced CD34-enriched bone marrow cells, vector proviruses were identified at three distinct sites within a window of 664 base pairs between leupaxin and zinc finger protein 91 (ZFP91). All three integrants of the CIS occurred within a CpG island between leupaxin and zinc finger protein 91 (ZFP91). We describe a novel CIS between leupaxin and ZFP91 in hematopoietic repopulating cells. Our data suggest that leupaxin and/or ZFP91 may play a role in hematopoietic repopulating cells.