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

C Baum; C von Kalle; F J T Staal; Z X Li; B Fehse; M Schmidt; F Weerkamp; Stefan Karlsson; G Wagemaker; D A Williams

doi:10.1016/j.ymthe.2003.10.013

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

C Baum, C von Kalle, F J T Staal, Z X Li, B Fehse, M Schmidt, F Weerkamp, Stefan Karlsson, G Wagemaker, D A Williams

Division of Molecular Medicine and Gene Therapy

Research output: Contribution to journal › Review article › peer-review

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.

Original language	English
Pages (from-to)	5-13
Journal	Molecular Therapy
Volume	9
Issue number	1
DOIs	https://doi.org/10.1016/j.ymthe.2003.10.013
Publication status	Published - 2004

Subject classification (UKÄ)

Medical Genetics and Genomics (including Gene Therapy)

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10.1016/j.ymthe.2003.10.013

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title = "Chance or necessity? Insertional mutagenesis in gene therapy and its consequences",

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 = "C Baum and {von Kalle}, C and Staal, {F J T} and Li, {Z X} and B Fehse and M Schmidt and F Weerkamp and Stefan Karlsson and G Wagemaker and Williams, {D A}",

year = "2004",

doi = "10.1016/j.ymthe.2003.10.013",

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journal = "Molecular Therapy",

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T1 - Chance or necessity? Insertional mutagenesis in gene therapy and its consequences

AU - Baum, C

AU - von Kalle, C

AU - Staal, F J T

AU - Li, Z X

AU - Fehse, B

AU - Schmidt, M

AU - Weerkamp, F

AU - Karlsson, Stefan

AU - Wagemaker, G

AU - Williams, D A

PY - 2004

Y1 - 2004

N2 - 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.

AB - 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.

U2 - 10.1016/j.ymthe.2003.10.013

DO - 10.1016/j.ymthe.2003.10.013

M3 - Review article

SN - 1525-0024

VL - 9

SP - 5

EP - 13

JO - Molecular Therapy

JF - Molecular Therapy

IS - 1

ER -

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

Abstract

Subject classification (UKÄ)

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