Acute myeloid leukemia is associated with retroviral gene transfer to hematopoietic progenitor cells in a rhesus macaque.
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.
Seggewiss
Ruth
R
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.
Pittaluga
Stefania
S
Adler
Rima L
RL
Guenaga
F Javier
FJ
Ferguson
Cole
C
Pilz
Ingo H
IH
Ryu
Byoung
B
Sorrentino
Brian P
BP
Young
W Scott
WS
Donahue
Robert E
RE
von Kalle
Christof
C
Nienhuis
Arthur W
AW
Dunbar
Cynthia E
CE
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
D049452:Green Fluorescent Proteins