Engraftment of MDR1 and NeoR gene-transduced hematopoietic cells after breast cancer chemotherapy

Jeffrey A. Moscow, Hui Huang, Charles Carter, Kenneth Hines, JoAnne Zujewski, Georgie Cusack, Cathy Chow, David Venzon, Brian Sorrentino, Yawen Chiang, Barry Goldspiel, Susan Leitman, Elizabeth J. Read, Andrea Abati, Michael M. Gottesman, Ira Pastan, Stephanie Sellers, Cynthia Dunbar, Kenneth H Cowan

Research output: Contribution to journalArticle

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Abstract

To determine whether the multidrug resistance gene MDR1 could act as a selectable marker in human subjects, we studied engraftment of peripheral blood progenitor cells (PBPCs) transduced with either MDR1 or the bacterial NeoR gene in six breast cancer patients. This study differed from previous MDR1 gene therapy studies in that patients received only PBPCs incubated in retroviral supernatants (no nonmanipulated PBPCs were infused), transduction of PBPCs was supported with autologous bone marrow stroma without additional cytokines, and a control gene (NeoR) was used for comparison with MDR1. Transduced PBPCs were infused after high-dose alkylating agent therapy and before chemotherapy with MDR-substrate drugs. We found that hematopoietic reconstitution can occur using only PBPCs incubated ex vivo, that the MDR1 gene product may play a role in engraftment, and that chemotherapy may selectively expand MDR1 gene-transduced hematopoietic cells relative to NeoR transduced cells in some patients.

Original languageEnglish (US)
Pages (from-to)52-61
Number of pages10
JournalBlood
Volume94
Issue number1
StatePublished - Jul 1 1999

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Chemotherapy
Blood Cells
Blood
Stem Cells
Genes
Breast Neoplasms
Drug Therapy
MDR Genes
Bacterial Genes
Gene therapy
Alkylating Agents
Genetic Therapy
Bone
Bone Marrow
Cytokines
Substrates
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Moscow, J. A., Huang, H., Carter, C., Hines, K., Zujewski, J., Cusack, G., ... Cowan, K. H. (1999). Engraftment of MDR1 and NeoR gene-transduced hematopoietic cells after breast cancer chemotherapy. Blood, 94(1), 52-61.

Engraftment of MDR1 and NeoR gene-transduced hematopoietic cells after breast cancer chemotherapy. / Moscow, Jeffrey A.; Huang, Hui; Carter, Charles; Hines, Kenneth; Zujewski, JoAnne; Cusack, Georgie; Chow, Cathy; Venzon, David; Sorrentino, Brian; Chiang, Yawen; Goldspiel, Barry; Leitman, Susan; Read, Elizabeth J.; Abati, Andrea; Gottesman, Michael M.; Pastan, Ira; Sellers, Stephanie; Dunbar, Cynthia; Cowan, Kenneth H.

In: Blood, Vol. 94, No. 1, 01.07.1999, p. 52-61.

Research output: Contribution to journalArticle

Moscow, JA, Huang, H, Carter, C, Hines, K, Zujewski, J, Cusack, G, Chow, C, Venzon, D, Sorrentino, B, Chiang, Y, Goldspiel, B, Leitman, S, Read, EJ, Abati, A, Gottesman, MM, Pastan, I, Sellers, S, Dunbar, C & Cowan, KH 1999, 'Engraftment of MDR1 and NeoR gene-transduced hematopoietic cells after breast cancer chemotherapy', Blood, vol. 94, no. 1, pp. 52-61.
Moscow JA, Huang H, Carter C, Hines K, Zujewski J, Cusack G et al. Engraftment of MDR1 and NeoR gene-transduced hematopoietic cells after breast cancer chemotherapy. Blood. 1999 Jul 1;94(1):52-61.
Moscow, Jeffrey A. ; Huang, Hui ; Carter, Charles ; Hines, Kenneth ; Zujewski, JoAnne ; Cusack, Georgie ; Chow, Cathy ; Venzon, David ; Sorrentino, Brian ; Chiang, Yawen ; Goldspiel, Barry ; Leitman, Susan ; Read, Elizabeth J. ; Abati, Andrea ; Gottesman, Michael M. ; Pastan, Ira ; Sellers, Stephanie ; Dunbar, Cynthia ; Cowan, Kenneth H. / Engraftment of MDR1 and NeoR gene-transduced hematopoietic cells after breast cancer chemotherapy. In: Blood. 1999 ; Vol. 94, No. 1. pp. 52-61.
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