Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2008 Mar;16(3):439-49.
doi: 10.1038/sj.mt.6300372. Epub 2008 Jan 29.

The MDS1-EVI1 gene complex as a retrovirus integration site: impact on behavior of hematopoietic cells and implications for gene therapy

Jean-Yves Métais  1 , Cynthia E Dunbar
Affiliations
Free article
Review

The MDS1-EVI1 gene complex as a retrovirus integration site: impact on behavior of hematopoietic cells and implications for gene therapy

Jean-Yves Métais et al. Mol Ther. 2008 Mar.
Free article

Abstract

Gene therapy trials have been performed with virus-based vectors that have the ability to integrate permanently into genomic DNA and thus allow prolonged expression of corrective genes after transduction of hematopoietic stem and progenitor cells. Adverse events observed during the X-linked severe combined immunodeficiency gene therapy trial revealed a significant risk of genotoxicity related to retrovirus vector integration and activation of adjacent proto-oncogenes, with several cases of T-cell leukemia linked to vector activation of the LMO2 gene. In patients with chronic granulomatous disease (CGD), rhesus macaques, and mice receiving hematopoietic stem and progenitor cells transduced with retrovirus vectors, a highly non-random pattern of vector integration has been reported. The most striking finding has been overrepresentation of integrations in one specific genomic locus, a complex containing the MDS1 and the EVI1 genes. Most evidence suggests that this overrepresentation is primarily due to a modification of primitive myeloid cell behavior by overexpression of EVI1 or MDS1-EVI1, as opposed to a specific predilection for integration at this site. Three different proteins can be produced from this complex locus: MDS1, MDS1-EVI1, and EVI1. This review will summarize current knowledge regarding this locus and its gene products, with specific focus on issues with relevance to gene therapy, leukemogenesis, and hematopoiesis. Insights into the mechanisms that result in altered hematopoiesis and leukemogenesis when this locus is dysregulated could improve the safety of gene therapy in the future.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

MeSH terms

LinkOut - more resources