Acute myeloid leukemia is associated with retroviral gene transfer to hematopoietic progenitor cells in a rhesus macaque
- 15 May 2006
- journal article
- Published by American Society of Hematology in Blood
- Vol. 107 (10) , 3865-3867
- https://doi.org/10.1182/blood-2005-10-4108
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.Keywords
This publication has 15 references indexed in Scilit:
- Insertional mutagenesis identifies genes that promote the immortalization of primary bone marrow progenitor cellsBlood, 2005
- Cooperating cancer-gene identification through oncogenic-retrovirus–induced insertional mutagenesisBlood, 2005
- Clonal Dominance of Hematopoietic Stem Cells Triggered by Retroviral Gene MarkingScience, 2005
- Distinct Genomic Integration of MLV and SIV Vectors in Primate Hematopoietic Stem and Progenitor CellsPLoS Biology, 2004
- Long-Term Clinical and Molecular Follow-up of Large Animals Receiving Retrovirally Transduced Stem and Progenitor Cells: No Progression to Clonal Hematopoiesis or LeukemiaMolecular Therapy, 2004
- Transient in vivo selection of transduced peripheral blood cells using antifolate drug selection in rhesus macaques that received transplants with hematopoietic stem cells expressing dihydrofolate reductase vectorsBlood, 2004
- LMO2 -Associated Clonal T Cell Proliferation in Two Patients after Gene Therapy for SCID-X1Science, 2003
- The Human Genome Browser at UCSCGenome Research, 2002
- Murine Leukemia Induced by Retroviral Gene MarkingScience, 2002
- A Rapid and Quantitative Assay to Estimate Gene Transfer into Retrovirally Transduced Hematopoietic Stem/Progenitor Cells Using a 96-Well Format PCR and Fluorescent Detection System Universal for MMLV-Based ProvirusesHuman Gene Therapy, 1996