title: Acute myeloid leukemia is associated with retroviral gene transfer to hematopoietic progenitor cells in a rhesus macaque.
abstract: We report, for the first time, a replication-defective retroviral vector-associated neoplasia in a nonhuman primate. Five years after transplantation with CD34+ cells transduced with a retroviral vector expressing enhanced green fluorescent protein (eGFP) and a drug-resistant variant of the dihydrofolate reductase gene (L22Y), a rhesus macaque developed a fatal myeloid sarcoma, a type of acute myeloid leukemia. Tumor cells contained 2 clonal vector insertions. One insertion was found in BCL2-A1, an antiapoptotic gene. This event suggests that currently available retroviral vectors may have long-term side effects, particularly in hematopoietic stem and progenitor cells.
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, NIH/DHHS, Bldg 10, CRC, Rm 4-5130, 10 Center Drive, MSC 1202, Bethesda, MD 20892, USA.
authors.forename: Ruth
authors.initials: R
authors.lastname: Seggewiss
authors.forename: Stefania
authors.initials: S
authors.lastname: Pittaluga
authors.forename: Rima L
authors.initials: RL
authors.lastname: Adler
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Guenaga
authors.forename: Cole
authors.initials: C
authors.lastname: Ferguson
authors.forename: Ingo H
authors.initials: IH
authors.lastname: Pilz
authors.forename: Byoung
authors.initials: B
authors.lastname: Ryu
authors.forename: Brian P
authors.initials: BP
authors.lastname: Sorrentino
authors.forename: W Scott
authors.initials: WS
authors.lastname: Young
authors.forename: Robert E
authors.initials: RE
authors.lastname: Donahue
authors.forename: Christof
authors.initials: C
authors.lastname: von Kalle
authors.forename: Arthur W
authors.initials: AW
authors.lastname: Nienhuis
authors.forename: Cynthia E
authors.initials: CE
authors.lastname: Dunbar
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics; D019650:Hematopoietic Stem Cell Mobilization; D007951:Leukemia, Myeloid / Q000235:genetics*; D008253:Macaca mulatta; D012190:Retroviridae / Q000235:genetics*; D033581:Stem Cell Transplantation
chemical_list: D049452:Green Fluorescent Proteins