|
|
Blood, 1 October 2005, Vol. 106, No. 7, pp. 2530-2533.
Prepublished online as a Blood First Edition Paper on June 2, 2005; DOI 10.1182/blood-2005-03-1115.
Previous Article | Table of Contents | Next Article 
NEOPLASIA Brief report
Recurrent retroviral vector integration at the Mds1/Evi1 locus in nonhuman primate hematopoietic cells
Boris Calmels,
Cole Ferguson,
Mikko O. Laukkanen,
Rima Adler,
Marion Faulhaber,
Hyeoung-Joon Kim,
Stephanie Sellers,
Peiman Hematti,
Manfred Schmidt,
Christof von Kalle,
Keiko Akagi,
Robert E. Donahue, and
Cynthia E. Dunbar
From the Hematology Branch, National Heart, Lung, and Blood Institute, Bethesda, MD; the Chonnam National University Hospital, Gwangju, Korea; the University of Freiburg, Germany; the Children's Hospital Research Foundation, Cincinnati, OH; and the Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD.
Recent reports linking insertional activation of LMO2 following gene therapy for X-linked severe combined immunodeficiency (X-SCID) have led to a re-evaluation of risks following gene therapy with retroviral vectors. In our analysis of 702 integration sites in rhesus macaques that underwent transplantation up to 7 years earlier with autologous CD34+ cells transduced with amphotropic murine leukemia virus (MLV)-derived retroviral vectors containing marker genes, we detected insertion into one locus, the Mds1/Evi1 region, a total of 14 times in 9 animals. Mds1/Evi1 integrations were observed stably long term, primarily in myeloid cells. We hypothesize that this over-representation likely results from an impact on the self-renewal and engraftment potential of CD34+ progenitor cells via insertional mutagenesis at this specific locus. There is no evidence of ongoing in vivo clonal expansion of the Mds1/Evi1 populations, and all animals are hematologically normal without evidence for leukemia. Characterization of integration sites in this relevant preclinical model provides critical information for gene therapy risk assessment as well as identification of genes controlling hematopoiesis. (Blood. 2005;106:2530-2533)

CiteULike Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
B. Cassani, E. Montini, G. Maruggi, A. Ambrosi, M. Mirolo, S. Selleri, E. Biral, I. Frugnoli, V. Hernandez-Trujillo, C. Di Serio, et al.
Integration of retroviral vectors induces minor changes in the transcriptional activity of T cells from ADA-SCID patients treated with gene therapy
Blood,
October 22, 2009;
114(17):
3546 - 3556.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y.-J. Kim, Y.-S. Kim, A. Larochelle, G. Renaud, T. G. Wolfsberg, R. Adler, R. E. Donahue, P. Hematti, B.-K. Hong, J. Roayaei, et al.
Sustained high-level polyclonal hematopoietic marking and transgene expression 4 years after autologous transplantation of rhesus macaques with SIV lentiviral vector-transduced CD34+ cells
Blood,
May 28, 2009;
113(22):
5434 - 5443.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. C. Beard, R. Sud, K. A. Keyser, C. Ironside, T. Neff, S. Gerull, G. D. Trobridge, and H.-P. Kiem
Long-term polyclonal and multilineage engraftment of methylguanine methyltransferase P140K gene-modified dog hematopoietic cells in primary and secondary recipients
Blood,
May 21, 2009;
113(21):
5094 - 5103.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. W. Nienhuis
Development of gene therapy for blood disorders
Blood,
May 1, 2008;
111(9):
4431 - 4444.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. Watanabe-Okochi, J. Kitaura, R. Ono, H. Harada, Y. Harada, Y. Komeno, H. Nakajima, T. Nosaka, T. Inaba, and T. Kitamura
AML1 mutations induced MDS and MDS/AML in a mouse BMT model
Blood,
April 15, 2008;
111(8):
4297 - 4308.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Cattoglio, G. Facchini, D. Sartori, A. Antonelli, A. Miccio, B. Cassani, M. Schmidt, C. von Kalle, S. Howe, A. J. Thrasher, et al.
Hot spots of retroviral integration in human CD34+ hematopoietic cells
Blood,
September 15, 2007;
110(6):
1770 - 1778.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
O. S. Kustikova, H. Geiger, Z. Li, M. H. Brugman, S. M. Chambers, C. A. Shaw, K. Pike-Overzet, D. d. Ridder, F. J. T. Staal, G. v. Keudell, et al.
Retroviral vector insertion sites associated with dominant hematopoietic clones mark "stemness" pathways
Blood,
March 1, 2007;
109(5):
1897 - 1907.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. E. Dunbar
The Yin and Yang of Stem Cell Gene Therapy: Insights into Hematopoiesis, Leukemogenesis, and Gene Therapy Safety
Hematology,
January 1, 2007;
2007(1):
460 - 465.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
U. Modlich, J. Bohne, M. Schmidt, C. von Kalle, S. Knoss, A. Schambach, and C. Baum
Cell-culture assays reveal the importance of retroviral vector design for insertional genotoxicity
Blood,
October 15, 2006;
108(8):
2545 - 2553.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Puglia, T. Wang, C. Smith-Snyder, M. Cote, M. Scher, J. N. Pelletier, S. John, C. B. Jonsson, and M. J. Roth
Revealing Domain Structure through Linker-Scanning Analysis of the Murine Leukemia Virus (MuLV) RNase H and MuLV and Human Immunodeficiency Virus Type 1 Integrase Proteins
J. Virol.,
October 1, 2006;
80(19):
9497 - 9510.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Seggewiss, S. Pittaluga, R. L. Adler, F. J. Guenaga, C. Ferguson, I. H. Pilz, B. Ryu, B. P. Sorrentino, W. S. Young III, R. E. Donahue, et al.
Acute myeloid leukemia is associated with retroviral gene transfer to hematopoietic progenitor cells in a rhesus macaque
Blood,
May 15, 2006;
107(10):
3865 - 3867.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. E. Boyd, Y.-Y. Xiao, K. Fan, A. Poholek, N. G. Copeland, N. A. Jenkins, and A. S. Perkins
Sox4 cooperates with Evi1 in AKXD-23 myeloid tumors via transactivation of proviral LTR
Blood,
January 15, 2006;
107(2):
733 - 741.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Du, N. A. Jenkins, and N. G. Copeland
Insertional mutagenesis identifies genes that promote the immortalization of primary bone marrow progenitor cells
Blood,
December 1, 2005;
106(12):
3932 - 3939.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|
|