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Previous Article | Table of Contents | Next Article 
Retrovirally marked CD34-enriched peripheral blood and bone marrow cells
contribute to long-term engraftment after autologous transplantation
CE Dunbar, M Cottler-Fox, JA O'Shaughnessy, S Doren, C Carter, R Berenson, S Brown, RC Moen, J Greenblatt and FM Stewart
Hematology Branch, National Heart, Lung, and Blood Institute, National
Institutes of Health, Bethesda, MD 20892-1652, USA.
We report here on a preliminary human autologous transplantation study of
retroviral gene transfer to bone marrow (BM) and peripheral blood
(PB)-derived CD34-enriched cells. Eleven patients with multiple myeloma or
breast cancer had cyclophosphamide and filgrastim-mobilized PB cells
CD34-enriched and transduced with a retroviral marking vector containing
the neomycin resistance gene, and CD34-enriched BM cells transduced with a
second marking vector also containing a neomycin resistance gene. After
high-dose conditioning therapy, both transduced cell populations were
reinfused and patients were followed over time for the presence of the
marker gene and any adverse effects related to the gene-transfer procedure.
All 10 evaluable patients had the marker gene detected at the time of
engraftment, and 3 of 9 patients had persistence of the marker gene for
greater than 18 months posttransplantation. The marker gene was detected in
multiple lineages, including granulocytes, T cells, and B cells. The source
of the marking was both the transduced PB graft and the BM graft, with a
suggestion of better long-term marking originating from the PB graft. The
steady- state levels of marking were low, with only 1:1000 to 1:10,000
cells positive. There was no toxicity noted, and patients did not develop
detectable replication-competent helper virus at any time
posttransplantation. These results suggest that mobilized PB cells may be
preferable to BM for gene therapy applications and that progeny of
mobilized peripheral blood cells can contribute long-term to engraftment of
multiple lineages.
Volume 85,
Issue 11,
pp. 3048-3057,
06/01/1995
Copyright © 1995 by The American Society of Hematology

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C. Lutzko, S. Kruth, A. C.G. Abrams-Ogg, K. Lau, L. Li, B. R. Clark, C. Ruedy, S. Nanji, R. Foster, D. Kohn, et al.
Genetically Corrected Autologous Stem Cells Engraft, But Host Immune Responses Limit Their Utility in Canine alpha -L-iduronidase Deficiency
Blood,
March 15, 1999;
93(6):
1895 - 1905.
[Abstract]
[Full Text]
[PDF]
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J. A Smith and B. R Goldspiel
Cancer gene therapy update
Journal of Oncology Pharmacy Practice,
March 1, 1999;
5(1):
7 - 21.
[Abstract]
[PDF]
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G. Guenechea, J.C. Segovia, B. Albella, M. Lamana, M. Ramirez, C. Regidor, M.N. Fernandez, and J.A. Bueren
Delayed Engraftment of Nonobese Diabetic/Severe Combined Immunodeficient Mice Transplanted With Ex Vivo-Expanded Human CD34+ Cord Blood Cells
Blood,
February 1, 1999;
93(3):
1097 - 1105.
[Abstract]
[Full Text]
[PDF]
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K. D. Bunting, K. J. Flynn, J. M. Riberdy, P. C. Doherty, and B. P. Sorrentino
Virus-specific immunity after gene therapy in a murine model of severe combined immunodeficiency
PNAS,
January 5, 1999;
96(1):
232 - 237.
[Abstract]
[Full Text]
[PDF]
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J. Povey, N. Weeratunge, C. Marden, A. Sehgal, A. Thrasher, and C. Casimir
Enhanced Retroviral Transduction of 5-Fluorouracil-Resistant Human Bone Marrow (Stem) Cells Using a Genetically Modified Packaging Cell Line
Blood,
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92(11):
4080 - 4089.
[Abstract]
[Full Text]
[PDF]
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A. J. Schilz, G. Brouns, O. G. Ottmann, D. Hoelzer, A. A. Fauser, A. J. Thrasher, and M. Grez
High Efficiency Gene Transfer to Human Hematopoietic SCID-Repopulating Cells Under Serum-Free Conditions
Blood,
November 1, 1998;
92(9):
3163 - 3171.
[Abstract]
[Full Text]
[PDF]
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J. C.M. van der Loo, H. Hanenberg, R. J. Cooper, F.-Y. Luo, E. N. Lazaridis, and D. A. Williams
Nonobese Diabetic/Severe Combined Immunodeficiency (NOD/SCID) Mouse as a Model System to Study the Engraftment and Mobilization of Human Peripheral Blood Stem Cells
Blood,
October 1, 1998;
92(7):
2556 - 2570.
[Abstract]
[Full Text]
[PDF]
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J.F. Tisdale, Y. Hanazono, S.E. Sellers, B.A. Agricola, M.E. Metzger, R.E. Donahue, and C.E. Dunbar
Ex Vivo Expansion of Genetically Marked Rhesus Peripheral Blood Progenitor Cells Results in Diminished Long-Term Repopulating Ability
Blood,
August 15, 1998;
92(4):
1131 - 1141.
[Abstract]
[Full Text]
[PDF]
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K. E. Pollok, H. Hanenberg, T. W. Noblitt, W. L. Schroeder, I. Kato, D. Emanuel, and D. A. Williams
High-Efficiency Gene Transfer into Normal and Adenosine Deaminase-Deficient T Lymphocytes Is Mediated by Transduction on Recombinant Fibronectin Fragments
J. Virol.,
June 1, 1998;
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4882 - 4892.
[Abstract]
[Full Text]
[PDF]
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P. Veena, C. M. Traycoff, D. A. Williams, J. McMahel, S. Rice, K. Cornetta, and E. F. Srour
Delayed Targeting of Cytokine-Nonresponsive Human Bone Marrow CD34+ Cells With Retrovirus-Mediated Gene Transfer Enhances Transduction Efficiency and Long-Term Expression of Transduced Genes
Blood,
May 15, 1998;
91(10):
3693 - 3701.
[Abstract]
[Full Text]
[PDF]
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D. Orlic, L. J. Girard, S. M. Anderson, L. C. Pyle, M. C. Yoder, H. E. Broxmeyer, and D. M. Bodine
Identification of Human and Mouse Hematopoietic Stem Cell Populations Expressing High Levels of mRNA Encoding Retrovirus Receptors
Blood,
May 1, 1998;
91(9):
3247 - 3254.
[Abstract]
[Full Text]
[PDF]
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A. Rambaldi, G. Borleri, G. Dotti, P. Bellavita, R. Amaru, A. Biondi, and T. Barbui
Innovative Two-Step Negative Selection of Granulocyte Colony-Stimulating Factor-Mobilized Circulating Progenitor Cells: Adequacy for Autologous and Allogeneic Transplantation
Blood,
March 15, 1998;
91(6):
2189 - 2196.
[Abstract]
[Full Text]
[PDF]
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M. Onodera, D. M. Nelson, A. Yachie, G. J. Jagadeesh, B. A. Bunnell, R. A. Morgan, and R. M. Blaese
Development of Improved Adenosine Deaminase Retroviral Vectors
J. Virol.,
March 1, 1998;
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1769 - 1774.
[Abstract]
[Full Text]
[PDF]
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A. K. Fielding, M. Maurice, F. J. Morling, F.-L. Cosset, and S. J. Russell
Inverse Targeting of Retroviral Vectors: Selective Gene Transfer in a Mixed Population of Hematopoietic and Nonhematopoietic Cells
Blood,
March 1, 1998;
91(5):
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[Abstract]
[Full Text]
[PDF]
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S. D. Lyman and S. E. W. Jacobsen
c-kit Ligand and Flt3 Ligand: Stem/Progenitor Cell Factors With Overlapping Yet Distinct Activities
Blood,
February 15, 1998;
91(4):
1101 - 1134.
[Full Text]
[PDF]
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D. von Laer, S. Thomsen, B. Vogt, M. Donath, J. Kruppa, A. Rein, W. Ostertag, and C. Stocking
Entry of Amphotropic and 10A1 Pseudotyped Murine Retroviruses Is Restricted in Hematopoietic Stem Cell Lines
J. Virol.,
February 1, 1998;
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1424 - 1430.
[Abstract]
[Full Text]
[PDF]
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L. Jin, H. Asano, and C. Anthony Blau
Stimulating Cell Proliferation Through the Pharmacologic Activation of c-kit
Blood,
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[Abstract]
[Full Text]
[PDF]
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B. Verhasselt, M. De Smedt, R. Verhelst, E. Naessens, and J. Plum
Retrovirally Transduced CD34++ Human Cord Blood Cells Generate T Cells Expressing High Levels of the Retroviral Encoded Green Fluorescent Protein Marker In Vitro
Blood,
January 15, 1998;
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431 - 440.
[Abstract]
[Full Text]
[PDF]
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M. Rosenzweig, D. F. Marks, D. Hempel, M. Heusch, G. Kraus, F. Wong-Staal, and R. P. Johnson
Intracellular Immunization of Rhesus CD34+ Hematopoietic Progenitor Cells With a Hairpin Ribozyme Protects T Cells and Macrophages From Simian Immunodeficiency Virus Infection
Blood,
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[Abstract]
[Full Text]
[PDF]
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H.-P. Kiem, S. Heyward, A. Winkler, J. Potter, J. M. Allen, A. D. Miller, and R. G. Andrews
Gene Transfer into Marrow Repopulating Cells: Comparison Between Amphotropic and Gibbon Ape Leukemia Virus Pseudotyped Retroviral Vectors in a Competitive Repopulation Assay in Baboons
Blood,
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90(11):
4638 - 4645.
[Abstract]
[Full Text]
[PDF]
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M. F.A. Bierhuizen, Y. Westerman, T. P. Visser, W. Dimjati, A. W. Wognum, and G. Wagemaker
Enhanced Green Fluorescent Protein as Selectable Marker of Retroviral-Mediated Gene Transfer in Immature Hematopoietic Bone Marrow Cells
Blood,
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3304 - 3315.
[Abstract]
[Full Text]
[PDF]
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L. Humeau, C. Chabannon, M. T. Firpo, P. Mannoni, C. Bagnis, M.-G. Roncarolo, and R. Namikawa
Successful Reconstitution of Human Hematopoiesis in the SCID-hu Mouse by Genetically Modified, Highly Enriched Progenitors Isolated From Fetal Liver
Blood,
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3496 - 3506.
[Abstract]
[Full Text]
[PDF]
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H. L. Malech, P. B. Maples, N. Whiting-Theobald, G. F. Linton, S. Sekhsaria, S. J. Vowells, F. Li, J. A. Miller, E. DeCarlo, S. M. Holland, et al.
Prolonged production of NADPH oxidase-corrected granulocytes after gene therapy of chronic granulomatous disease
PNAS,
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[Abstract]
[Full Text]
[PDF]
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E. Conneally, J. Cashman, A. Petzer, and C. Eaves
Expansion in vitro of transplantable human cord blood stem cells demonstrated using a quantitative assay of their lympho-myeloid repopulating activity in nonobese diabetic-scid/scid mice
PNAS,
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[Abstract]
[Full Text]
[PDF]
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D. A. Persons, J. A. Allay, E. R. Allay, R. J. Smeyne, R. A. Ashmun, B. P. Sorrentino, and A. W. Nienhuis
Retroviral-Mediated Transfer of the Green Fluorescent Protein Gene Into Murine Hematopoietic Cells Facilitates Scoring and Selection of Transduced Progenitors In Vitro and Identification of Genetically Modified Cells In Vivo
Blood,
September 1, 1997;
90(5):
1777 - 1786.
[Abstract]
[Full Text]
[PDF]
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E. L.W. Kittler, S. O. Peters, R. B. Crittenden, M. E. Debatis, H. S. Ramshaw, F. M. Stewart, and P. J. Quesenberry
Cytokine-Facilitated Transduction Leads to Low-Level Engraftment in Nonablated Hosts
Blood,
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865 - 872.
[Abstract]
[Full Text]
[PDF]
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I. Rappold, B. L. Ziegler, I. Kohler, S. Marchetto, O. Rosnet, D. Birnbaum, P. J. Simmons, A. C.W. Zannettino, B. Hill, S. Neu, et al.
Functional and Phenotypic Characterization of Cord Blood and Bone Marrow Subsets Expressing FLT3 (CD135) Receptor Tyrosine Kinase
Blood,
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111 - 125.
[Abstract]
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C. Bagnis and P. Mannoni
Stem Cell-Based Gene Therapy
Oncologist,
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196 - 202.
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R.V.B. Emmons, S. Doren, J. Zujewski, M. Cottler-Fox, C.S. Carter, K. Hines, J.A. O'Shaughnessy, S.F. Leitman, J.J. Greenblatt, K. Cowan, et al.
Retroviral Gene Transduction of Adult Peripheral Blood or Marrow-Derived CD34+ Cells for Six Hours Without Growth Factors or on Autologous Stroma Does Not Improve Marking Efficiency Assessed In Vivo
Blood,
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4040 - 4046.
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C. A. Blau, K. R. Peterson, J. G. Drachman, and D. M. Spencer
A proliferation switch for genetically modified cells
PNAS,
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L.B. To, D.N. Haylock, P.J. Simmons, and C.A. Juttner
The Biology and Clinical Uses of Blood Stem Cells
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G. Bauer, P. Valdez, K. Kearns, I. Bahner, S. F. Wen, J. A. Zaia, and D. B. Kohn
Inhibition of Human Immunodeficiency Virus-1 (HIV-1) Replication After Transduction of Granulocyte Colony-Stimulating Factor-Mobilized CD34+ Cells From HIV-1-Infected Donors Using Retroviral Vectors Containing Anti-HIV-1 Genes
Blood,
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[Abstract]
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P. W. Hargrove, E. F. Vanin, G. J. Kurtzman, and A. W. Nienhuis
High-Level Globin Gene Expression Mediated by a Recombinant Adeno-Associated Virus Genome That Contains the 3' gamma Globin Gene Regulatory Element and Integrates as Tandem Copies in Erythroid Cells
Blood,
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[Abstract]
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W. M. Weil, G. F. Linton, N. Whiting-Theobald, S. J. Vowells, S. P. Rafferty, F. Li, and H. L. Malech
Genetic Correction of p67phox Deficient Chronic Granulomatous Disease Using Peripheral Blood Progenitor Cells as a Target for Retrovirus Mediated Gene Transfer
Blood,
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[Abstract]
[Full Text]
[PDF]
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D. Dilloo, D. Rill, C. Entwistle, M. Boursnell, W. Zhong, W. Holden, M. Holladay, S. Inglis, and M. Brenner
A Novel Herpes Vector for the High-Efficiency Transduction of Normal and Malignant Human Hematopoietic Cells
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[Abstract]
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C. A. Blau, T. Neff, and T. Papayannopoulou
Cytokine Prestimulation as a Gene Therapy Strategy: Implications for Using the MDR1 Gene as a Dominant Selectable Marker
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J. Reiser, G. Harmison, S. Kluepfel-Stahl, R. O. Brady, S. Karlsson, and M. Schubert
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C. Bordignon, L. D. Notarangelo, N. Nobili, G. Ferrari, G. Casorati, P. Panina, E. Mazzolari, D. Maggioni, C. Rossi, P. Servida, et al.
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A. Kessinger
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