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Science 20 May 2005:
Vol. 308. no. 5725, pp. 1171 - 1174
DOI: 10.1126/science.1105063
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Reports

Clonal Dominance of Hematopoietic Stem Cells Triggered by Retroviral Gene Marking

Olga Kustikova,1* Boris Fehse,1* Ute Modlich,3 Min Yang,3 Jochen Düllmann,2 Kenji Kamino,4 Nils von Neuhoff,4 Brigitte Schlegelberger,4 Zhixiong Li,3{dagger} Christopher Baum3,5{dagger}

Gene marking with replication-defective retroviral vectors has been used for more than 20 years to track the in vivo fate of cell clones. We demonstrate that retroviral integrations themselves may trigger nonmalignant clonal expansion in murine long-term hematopoiesis. All 29 insertions recovered from clones dominating in serially transplanted recipients affected loci with an established or potential role in the self-renewal or survival of hematopoietic stem cells. Transcriptional dysregulation occurred in all 12 insertion sites analyzed. These findings have major implications for diagnostic gene marking and the discovery of genes regulating stem cell turnover.

1 Bone Marrow Transplantation, University Hospital Eppendorf, Martinistraße 52, 20251 Hamburg, Germany.
2 Institute for Anatomy II: Experimental Morphology, University Hospital Eppendorf, Martinistraße 52, 20251 Hamburg, Germany.
3 Department of Hematology, Hemostaseology, and Oncology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany.
4 Institute of Cellular and Molecular Pathology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany.
5 Division of Experimental Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229–3039, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed: E-mail: baum.christopher{at}mh-hannover.de (C.B.); li.zhixiong{at}mh-hannover.de (Z.L.)

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Science. ISSN 0036-8075 (print), 1095-9203 (online)