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Blood, 15 May 2006, Vol. 107, No. 10, pp. 3865-3867.
Prepublished online as a Blood First Edition Paper on January 26, 2006; DOI 10.1182/blood-2005-10-4108.
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GENE THERAPY Brief report
Acute myeloid leukemia is associated with retroviral gene transfer to hematopoietic progenitor cells in a rhesus macaque
Ruth Seggewiss,
Stefania Pittaluga,
Rima L. Adler,
F. Javier Guenaga,
Cole Ferguson,
Ingo H. Pilz,
Byoung Ryu,
Brian P. Sorrentino,
W. Scott Young, III,
Robert E. Donahue,
Christof von Kalle,
Arthur W. Nienhuis, and
Cynthia E. Dunbar
From the Hematology Branch, National Heart, Lung, and Blood Institute (NHLBI), the Hematopathology Section, National Cancer Institute (NCI), and the Section on Neural Gene Expression, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services (NIH/DHHS), Bethesda, MD; the Division of Experimental Hematology, Hematology-Oncology, St Jude's Children's Research Hospital, Memphis, TN; the University of Freiburg, Department of Medicine I, Freiburg, Germany; and the Children's Hospital Research Foundation, Molecular and Gene Therapy Program, Cincinnati, OH.
We report, for the first time, a replication-defective retroviral vectorassociated 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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