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

• Published in: Blood 2006-05, Vol.107 (10), p.3865-3867
• Main Authors: Seggewiss, Ruth, Pittaluga, Stefania, Adler, Rima L., Guenaga, F. Javier, Ferguson, Cole, Pilz, Ingo H., Ryu, Byoung, Sorrentino, Brian P., Young, W. Scott, Donahue, Robert E., von Kalle, Christof, Nienhuis, Arthur W., Dunbar, Cynthia E.
• Format: Article
• Language: English
• Subjects: Animals; Animals, Genetically Modified; Biological and medical sciences; Gene Therapy; Gene Transfer Techniques; Green Fluorescent Proteins - genetics; Hematologic and hematopoietic diseases; Hematopoietic Stem Cell Mobilization; Leukemia, Myeloid - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Macaca mulatta; Medical sciences; Retroviridae - genetics; Stem Cell Transplantation
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2005-10-4108

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.