Ex vivo expansion of retrovirally transduced primate CD34+ cells results in overrepresentation of clones with MDS1/EVI1 insertion sites in the myeloid lineage after transplantation.

ABSTRACT: Activation of proto-oncogenes by retroviral insertion is an important issue delaying clinical development of gene therapy. We have reported the nonrandom persistence of hematopoietic clones with vector insertions within the MDS1/EVI1 locus following transplantation of rhesus macaques. We now ask whether prolonged culture of transduced CD34(+) cells before transplantation selects for clones with insertions in the MDS1/EVI11 or other proto-oncogene loci. CD34(+) cells were transduced with standard retroviral vectors for 4 days and then continued in culture for an additional 6 days before transplantation. A 15% of insertions identified in granulocytes 6 months post-transplant were in MDS1/EVI11, significantly increased compared to the frequency in animals transplanted with cells immediately f

SUBMITTER: Sellers S 

PROVIDER: S-EPMC2956935 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature