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

ABSTRACT: 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.

SUBMITTER: Seggewiss R

PROVIDER: S-EPMC1895280 | biostudies-literature | 2006 May

REPOSITORIES: biostudies-literature

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

Seggewiss Ruth R 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

Blood 20060126 10

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, ...[more]

PMID: 16439674

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