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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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Submitted October 14, 2005
Accepted January 13, 2006
Acute myeloid leukemia associated with retroviral gene transfer to hematopoietic progenitor cells of a rhesus macaque
Ruth Seggewiss, Stefania Pittaluga, Rima L Adler, F J Guenaga, Cole Ferguson, Ingo Pilz, Byoung Ryu, Brian P Sorrentino, W S Young, Robert E Donahue, Christof von Kalle, Arthur W Nienhuis, and Cynthia E Dunbar*
Hematology Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA
Hematopathology Section, National Cancer Institute, NIH, Bethesda, MD, USA
Department of Medicine I, University of Freiburg, Freiburg, Germany
Division of Experimental Hematology, St. Jude Children's Research Hospital, Division of Experimental Hematology, Memphis, TN, USA
Section on Neural Gene Expression, National Institute of Mental Health, NIH/DHHS, Bethesda, MD, USA
Department of Medicine I, University of Freiburg, Freiburg, Germany; Molecular and Gene Therapy Program, Children's Hospital Research Foundation, Cincinnati, OH, USA
* Corresponding author; email: dunbarc{at}nhlbi.nih.gov.
We report for the first time a replication-defective retroviral vector-associated neoplasia in a non-human primate. Five years after transplantation with CD34+ cells transduced with a retroviral vector expressing eGFP and a drug-resistant variant of the dihydrofolate reductase gene, a rhesus macaque developed a fatal myeloid sarcoma, a type of acute myeloid leukemia. Tumor cells contained two clonal vector insertions. One insertion was found in BCL-2A1, an anti-apoptotic 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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