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19 results on '"Adler, Rima"'

1. Sustained high-level polyclonal hematopoietic marking and transgene expression 4 years after autologous transplantation of rhesus macaques with SIV lentiviral vector–transduced CD34+ cells

Author

Kim, Yoo-Jin, Kim, Yoon-Sang, Larochelle, Andre, Renaud, Gabriel, Wolfsberg, Tyra G., Adler, Rima, Donahue, Robert E., Hematti, Peiman, Hong, Bum-Kee, Roayaei, Jean, Akagi, Keiko, Riberdy, Janice M., Nienhuis, Arthur W., Dunbar, Cynthia E., and Persons, Derek A.

Published
2009
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2. Successful treatment of canine leukocyte adhesion deficiency by foamy virus vectors

Author

Bauer, Thomas R, Jr, Allen, James M, Hai, Mehreen, Tuschong, Laura M, Khan, Iram F, Olson, Erik M, Adler, Rima L, Burkholder, Tanya H, Gu, Yu-chen, Russell, David W, and Hickstein, Dennis D

Subjects
Leukocyte disorders -- Genetic aspects, Leukocyte disorders -- Care and treatment, Genetic vectors -- Usage, Immunodeficiency -- Genetic aspects, Immunodeficiency -- Care and treatment, Gene therapy -- Usage, Gene therapy -- Health aspects, Gene mutations -- Research, Gene mutations -- Health aspects
Abstract

Author(s): Thomas R Bauer, Jr [1]; James M Allen [2]; Mehreen Hai [1]; Laura M Tuschong [1]; Iram F Khan [2]; Erik M Olson [2]; Rima L Adler [1]; Tanya [...]

Published
2008
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3. Ex Vivo Expansion of Retrovirally Transduced Primate CD34+ Cells Results in Overrepresentation of Clones With MDS1/EVI1 Insertion Sites in the Myeloid Lineage After Transplantation

Author

Sellers, Stephanie, primary, Gomes, Theotonius J, additional, Larochelle, Andre, additional, Lopez, Rebecca, additional, Adler, Rima, additional, Krouse, Allen, additional, Donahue, Robert E, additional, Childs, Richard W, additional, and Dunbar, Cynthia E, additional

Published
2010
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8. Recurrent retroviral vector integration at the Mds1/Evi1 locus in nonhuman primate hematopoietic cells

Author

Calmels, Boris, primary, Ferguson, Cole, additional, Laukkanen, Mikko O., additional, Adler, Rima, additional, Faulhaber, Marion, additional, Kim, Hyeoung-Joon, additional, Sellers, Stephanie, additional, Hematti, Peiman, additional, Schmidt, Manfred, additional, von Kalle, Christof, additional, Akagi, Keiko, additional, Donahue, Robert E., additional, and Dunbar, Cynthia E., additional

Published
2005
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9. Distinct Genomic Integration of MLV and SIV Vectors in Primate Hematopoietic Stem and Progenitor Cells

Author

Hematti, Peiman, primary, Hong, Bum-Kee, additional, Ferguson, Cole, additional, Adler, Rima, additional, Hanawa, Hideki, additional, Sellers, Stephanie, additional, Holt, Ingeborg E, additional, Eckfeldt, Craig E, additional, Sharma, Yugal, additional, Schmidt, Manfred, additional, von Kalle, Christof, additional, Persons, Derek A, additional, Billings, Eric M, additional, Verfaillie, Catherine M, additional, Nienhuis, Arthur W, additional, Wolfsberg, Tyra G, additional, Dunbar, Cynthia E, additional, and Calmels, Boris, additional

Published
2004
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12. Long-Term Clinical and Molecular Follow-up of Large Animals Receiving Retrovirally Transduced Stem and Progenitor Cells: No Progression to Clonal Hematopoiesis or Leukemia

Author

Kiem, Hans-Peter, primary, Sellers, Stephanie, additional, Thomasson, Bobbie, additional, Morris, Julia C, additional, Tisdale, John F, additional, Horn, Peter A, additional, Hematti, Peiman, additional, Adler, Rima, additional, Kuramoto, Ken, additional, Calmels, Boris, additional, Bonifacino, Aylin, additional, Hu, Jiong, additional, von Kalle, Christof, additional, Schmidt, Manfred, additional, Sorrentino, Brian, additional, Nienhuis, Arthur, additional, Blau, C.Anthony, additional, Andrews, Robert G, additional, Donahue, Robert E, additional, and Dunbar, Cynthia E, additional

Published
2004
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14. Recurrent retroviral vector integration at the Mds1/Evi1locus in nonhuman primate hematopoietic cells

Author

Calmels, Boris, Ferguson, Cole, Laukkanen, Mikko O., Adler, Rima, Faulhaber, Marion, Kim, Hyeoung-Joon, Sellers, Stephanie, Hematti, Peiman, Schmidt, Manfred, von Kalle, Christof, Akagi, Keiko, Donahue, Robert E., and Dunbar, Cynthia E.

Abstract

Recent reports linking insertional activation of LMO2following 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/Evi1region, a total of 14 times in 9 animals. Mds1/Evi1integrations 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/Evi1populations, 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)

Published
2005
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16. Acute myeloid leukemia is associated with retroviral gene transfer to hematopoietic progenitor cells in a rhesus macaque

Author

Seggewiss, Ruth, Pittaluga, Stefania, Adler, Rima L., Guenaga, F. Javier, Ferguson, Cole, Pilz, Ingo H., Ryu, Byoung, Sorrentino, Brian P., Young, W. Scott, Donahue, Robert E., von Kalle, Christof, Nienhuis, Arthur W., and Dunbar, Cynthia E.

Abstract

We report, for the first time, a replication-defective retroviral vector–associated neoplasia in a nonhuman primate. Five years after transplantation with CD34+cells transduced with a retroviral vector expressing enhanced green fluorescent protein (eGFP)and a drug-resistant variant of the dihydrofolate reductase gene (L22Y), a rhesus macaque developed a fatal myeloid sarcoma, a type of acute myeloid leukemia. Tumor cells contained 2 clonal vector insertions. One insertion was found in BCL2-A1, an antiapoptotic gene. This event suggests that currently available retroviral vectors may have long-term side effects, particularly in hematopoietic stem and progenitor cells.

Published
2006
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17. Potential Large Animal Models for Gene Therapy of Human Genetic Diseases of Immune and Blood Cell Systems

Author

Bauer, Thomas R., Adler, Rima L., and Hickstein, Dennis D.

Abstract

Genetic mutations involving the cellular components of the hematopoietic system—red blood cells, white blood cells, and platelets—manifest clinically as anemia, infection, and bleeding. Although gene targeting has recapitulated many of these diseases in mice, these murine homologues are limited as translational models by their small size and brief life span as well as the fact that mutations induced by gene targeting do not always faithfully reflect the clinical manifestations of such mutations in humans. Many of these limitations can be overcome by identifying large animals with genetic diseases of the hematopoietic system corresponding to their human disease counterparts. In this article, we describe human diseases of the cellular components of the hematopoietic system that have counterparts in large animal species, in most cases carrying mutations in the same gene (CD18 in leukocyte adhesion deficiency) or genes in interacting proteins (DNA cross-link repair 1C protein and protein kinase, DNA-activated catalytic polypeptide in radiation-sensitive severe combined immunodeficiency). Furthermore, we describe the potential of these animal models to serve as disease-specific preclinical models for testing the efficacy and safety of clinical interventions such as hematopoietic stem cell transplantation or gene therapy before their use in humans with the corresponding disease.

Published
2009
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18. Ex Vivo Expansion of Retrovirally Transduced Primate CD34+ Cells Results in Overrepresentation of Clones With MDS1/EVI1 Insertion Sites in the Myeloid Lineage After Transplantation.

Author

Sellers, Stephanie, Gomes, Theotonius J., Larochelle, Andre, Lopez, Rebecca, Adler, Rima, Krouse, Allen, Donahue, Robert E., Childs, Richard W., and Dunbar, Cynthia E.

Subjects
*RETROVIRUS diseases, *CELL transplantation, *HEMATOPOIETIC stem cells, *MOLECULAR genetics, *MOLECULAR cloning, *GENE expression, *GENETIC transduction, *GENE therapy
Abstract

Activation of proto-oncogenes by retroviral insertion is an important issue delaying clinical development of gene therapy. We have reported the nonrandom persistence of hematopoietic clones with vector insertions within the MDS1/EVI1 locus following transplantation of rhesus macaques. We now ask whether prolonged culture of transduced CD34+ cells before transplantation selects for clones with insertions in the MDS1/EVI11 or other proto-oncogene loci. CD34+ cells were transduced with standard retroviral vectors for 4 days and then continued in culture for an additional 6 days before transplantation. A 15% of insertions identified in granulocytes 6 months post-transplant were in MDS1/EVI11, significantly increased compared to the frequency in animals transplanted with cells immediately following transduction. MDS1/EVI1 clones became more dominant over time post-transplantation in one animal that was followed long term, accompanied by an increased overall copy number of vector-containing granulocytes, with one MDS1/EVI1 clone eventually accounting for 100% of transduced granulocytes and marrow colony-forming unit (CFU). This vector insertion increased the expression of Evi1 mRNA. There was no overrepresentation of MDS1/EVI1 insertions contributing to lymphoid lineages. Strategies involving prolonged ex vivo expansion of transduced cells may increase the risk of genotoxicity. [ABSTRACT FROM AUTHOR]

Published
2010
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19. 387. Myeloid Sarcoma Associated with Gene Marking of Hematopoietic Stem Cells in a Rhesus Macaque

Author

Seggewiss, Ruth, Pittaluga, Stefania, Adler, Rima, Ferguson, Cole, Vanin, Elio F., Kelly, Patrick F., Donahue, Robert E., Sorrentino, Brian P., Nienhuis, Arthur W., and Dunbar, Cynthia E.

Subjects
*HEMATOPOIETIC stem cells
Abstract

An abstract of the article "Myeloid Sarcoma Associated with Gene Marking of Hematopoietic Stem Cells in a Rhesus Macaque," by Ruth Seggewiss, Stefania Pittaluga, Rima Adler, Cole Ferguson, Elio F. Vanin, Patrick F. Kelly, Robert E. Donahue, Brian P. Sorrentino and Arthur W. Nienhuis is presented.

Published
2005
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