Retroviral vector integration occurs in preferred genomic targets of human bone marrow-repopulating cells

Stephanie Laufs, Bernhard Gentner, K. Zsuzsanna Nagy, Anna Jauch, Axel Benner, Sonja Naundorf, Klaus Kuehlcke, Bernhard Schiedlmeier, Anthony D. Ho, W. Jens Zeller, Stefan Fruehauf

Research output: Contribution to journalArticle

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Abstract

Increasing use of hematopoietic stem cells for retroviral vector-mediated gene therapy and recent reports on insertional mutagenesis in mice and humans have created intense interest to characterize vector integrations on a genomic level. We studied retrovirally transduced human peripheral blood progenitor cells with bone marrow-repopulating ability in immune-deficient mice. By using a highly sensitive and specific ligation-mediated polymerase chain reaction (PCR) followed by sequencing of vector integration sites, we found a multitude of simultaneously active human stem cell clones 8 weeks after transplantation. Vector integrations occurred with significantly increased frequency into chromosomes 17 and 19 and into specific regions of chromosomes 6, 13, and 16, although most of the chromosomes were targeted. Preferred genomic target sites have previously only been reported for wild-type retroviruses. Our findings reveal for the first time that retroviral vector integration into human marrow-repopulating cells can be nonrandom (P = .000 37).

Original languageEnglish
Pages (from-to)2191-2198
Number of pages8
JournalBlood
Volume101
Issue number6
DOIs
Publication statusPublished - Mar 15 2003

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Bone Marrow Cells
Bone
Chromosomes
Stem cells
Stem Cells
Bone Marrow
Chromosomes, Human, Pair 19
Chromosomes, Human, Pair 16
Chromosomes, Human, Pair 13
Chromosomes, Human, Pair 17
Chromosomes, Human, Pair 6
Insertional Mutagenesis
Retroviridae
Hematopoietic Stem Cells
Gene therapy
Mutagenesis
Genetic Therapy
Polymerase chain reaction
Ligation
Blood Cells

ASJC Scopus subject areas

  • Hematology

Cite this

Retroviral vector integration occurs in preferred genomic targets of human bone marrow-repopulating cells. / Laufs, Stephanie; Gentner, Bernhard; Nagy, K. Zsuzsanna; Jauch, Anna; Benner, Axel; Naundorf, Sonja; Kuehlcke, Klaus; Schiedlmeier, Bernhard; Ho, Anthony D.; Zeller, W. Jens; Fruehauf, Stefan.

In: Blood, Vol. 101, No. 6, 15.03.2003, p. 2191-2198.

Research output: Contribution to journalArticle

Laufs, S, Gentner, B, Nagy, KZ, Jauch, A, Benner, A, Naundorf, S, Kuehlcke, K, Schiedlmeier, B, Ho, AD, Zeller, WJ & Fruehauf, S 2003, 'Retroviral vector integration occurs in preferred genomic targets of human bone marrow-repopulating cells', Blood, vol. 101, no. 6, pp. 2191-2198. https://doi.org/10.1182/blood-2002-02-0627
Laufs, Stephanie ; Gentner, Bernhard ; Nagy, K. Zsuzsanna ; Jauch, Anna ; Benner, Axel ; Naundorf, Sonja ; Kuehlcke, Klaus ; Schiedlmeier, Bernhard ; Ho, Anthony D. ; Zeller, W. Jens ; Fruehauf, Stefan. / Retroviral vector integration occurs in preferred genomic targets of human bone marrow-repopulating cells. In: Blood. 2003 ; Vol. 101, No. 6. pp. 2191-2198.
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