Acute myeloid leukemia is associated with retroviral gene transfer to hematopoietic progenitor cells in a rhesus macaque

被引:94
作者
Seggewiss, Ruth
Pittaluga, Stefania
Adler, Rima L.
Guenaga, F. Javier
Ferguson, Cole
Pilz, Ingo H.
Ryu, Byoung
Sorrentino, Brian P.
Young, W. Scott, III
Donahue, Robert E.
von Kalle, Christof
Nienhuis, Arthur W.
Dunbar, Cynthia E.
机构
[1] NHLBI, Hematol Branch, NIH, DHHS, Bethesda, MD 20892 USA
[2] NCI, Hematopathol Sect, Bethesda, MD 20892 USA
[3] NIMH, Sect Neural Gene Express, NIH, DHHS, Bethesda, MD 20892 USA
[4] St Jude Childrens Hosp, Div Expt Hematol Hematol Oncol, Memphis, TN 38105 USA
[5] Univ Freiburg, Dept Med 1, Freiburg, Germany
[6] Childrens Hosp Res Fdn, Mol & Gene Therapy Program, Cincinnati, OH 45229 USA
关键词
D O I
10.1182/blood-2005-10-4108
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
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页码:3865 / 3867
页数:3
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