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Chance or necessity? Insertional mutagenesis in gene therapy and its consequences

Baum, C; von Kalle, C; Staal, F J T; Li, Z X; Fehse, B; Schmidt, M; Weerkamp, F; Karlsson, Stefan LU ; Wagemaker, G and Williams, D A (2004) In Molecular Therapy 9(1). p.5-13
Abstract
Recently, unusual forms of leukemias have developed as complications following retroviral transfer of potentially therapeutic genes into hematopoietic cells. A crucial component in the pathogenesis of these complications was the upregulation of a cellular proto-oncogene by random insertion of the retroviral gene transfer vector. These findings have great implications for the genetic manipulation of somatic stem cells in medicine. This review discusses the extent to which the random oncogene activation may have required disease-specific stimuli of the transgene and the hematopoietic milieu to become leukemogenic. Based on these considerations, we propose approaches to risk prediction and prevention.
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Therapy
volume
9
issue
1
pages
5 - 13
publisher
Nature Publishing Group
external identifiers
  • wos:000188659300007
  • pmid:14741772
  • scopus:10744233606
ISSN
1525-0024
DOI
10.1016/j.ymthe.2003.10.013
language
English
LU publication?
yes
id
be94cc16-1003-4393-afe5-84f0bd2e7eda (old id 288600)
date added to LUP
2007-10-16 16:47:11
date last changed
2017-12-10 03:50:48
@article{be94cc16-1003-4393-afe5-84f0bd2e7eda,
  abstract     = {Recently, unusual forms of leukemias have developed as complications following retroviral transfer of potentially therapeutic genes into hematopoietic cells. A crucial component in the pathogenesis of these complications was the upregulation of a cellular proto-oncogene by random insertion of the retroviral gene transfer vector. These findings have great implications for the genetic manipulation of somatic stem cells in medicine. This review discusses the extent to which the random oncogene activation may have required disease-specific stimuli of the transgene and the hematopoietic milieu to become leukemogenic. Based on these considerations, we propose approaches to risk prediction and prevention.},
  author       = {Baum, C and von Kalle, C and Staal, F J T and Li, Z X and Fehse, B and Schmidt, M and Weerkamp, F and Karlsson, Stefan and Wagemaker, G and Williams, D A},
  issn         = {1525-0024},
  language     = {eng},
  number       = {1},
  pages        = {5--13},
  publisher    = {Nature Publishing Group},
  series       = {Molecular Therapy},
  title        = {Chance or necessity? Insertional mutagenesis in gene therapy and its consequences},
  url          = {http://dx.doi.org/10.1016/j.ymthe.2003.10.013},
  volume       = {9},
  year         = {2004},
}