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Cited by 270

The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.

Hot spots of retroviral integration in human CD34+ hematopoietic cells

Cattoglio, Claudia, Facchini, Giulia, Sartori, Daniela, Antonelli, Antonella, Miccio, Annarita, Cassani, Barbara, Schmidt, Manfred, von Kalle, Christof, Howe, Steve, Thrasher, Adrian J., Aiuti, Alessandro, Ferrari, Giuliana, Recchia, Alessandra, Mavilio, Fulvio·2007·Blood

Abstract

Insertional oncogenesis is a possible consequence of the integration of gamma-retroviral (RV) or lentiviral (LV) vectors into the human genome. RV common insertion sites (CISs) have been identified in hematopoietic malignancies and in the nonmalignant progeny of transduced hematopoietic stem/progenitor cells (HSCs), possibly as a consequence of clonal selection in vivo. We have mapped a large number of RV and LV integrations in human CD34+ HSCs, transduced in vitro and analyzed without selection. Recurrent insertion sites (hot spots) account for more than 21% of the RV integration events, while they are significantly less frequent in the case of LV vectors. RV but not LV hot spots are highly enriched in proto-oncogenes, cancer-associated CISs, and growth-controlling genes, indicating that at least part of the biases observed in the HSC progeny in vivo are characteristics of RV integration, already present in nontransplanted cells. Genes involved in hematopoietic and immune system development are targeted at high frequency and enriched in hot spots, suggesting that the CD34+ gene expression program is instrumental in directing RV integration. The lower propensity of LV vectors for integrating in potentially dangerous regions of the human genome may be a factor determining a better safety profile for gene therapy applications.

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Crossref · 10.1182/blood-2007-01-068759

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Metadata

Authors
Cattoglio, C., Facchini, G., Sartori, D., Antonelli, A., Miccio, A., Cassani, B., Schmidt, M., von Kalle, C., Howe, S., Thrasher, A. J., Aiuti, A., Ferrari, G., Recchia, A., & Mavilio, F.
Venue
Blood
Published
2007-09-15
Volume
110
Issue
6
Pages
1770-1778
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
OpenAlex
W2009078306
Cited by
270
References
5
FWCI
14.23
Type
journal article
Language
en
Open access
closed

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