Retroviral transfer and expression of the human multiple drug resistance (MDR) gene in peripheral blood progenitor cells.
The multiple drug resistance (MDR) gene P-glycoprotein product is a transmembrane efflux pump that prevents toxicity of a variety of chemotherapeutic agents, including the anthracyclines, Vinca alkaloids, podophyllins, and taxol. The bone marrow toxicity of these drugs is due to the low or absent expression of MDR in marrow cells. Transfer and expression of the human MDR gene into bone marrow progenitors should prevent this toxicity. We report here the efficient transfer and expression of the MDR gene by retroviral-mediated gene transfer into CD34(+) cells isolated from peripheral blood progenitor cells (PBPCs), comparable to that obtained using bone marrow-derived progenitors. Optimal MDR transduction of these PBPC-derived cells requires exposure to growth factors and a period of preincubation. In addition, we demonstrate that we can transduce up to 100% of progenitor cells derived from PBPCs and can protect up to 25% of these progenitors from a dose of taxol toxic to untransduced controls.
Ward
M
M
Columbia University, College of Physicians and Surgeons, Department of Genetics and Development and Department of Medicine, New York, New York 10032, USA.
Pioli
P
P
Ayello
J
J
Reiss
R
R
Urzi
G
G
Richardson
C
C
Hesdorffer
C
C
Bank
A
A
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D018952:Antigens, CD34 / Q000032:analysis; D019008:Drug Resistance, Neoplasm; D018014:Gene Transfer Techniques; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D017239:Paclitaxel / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012190:Retroviridae / Q000235:genetics*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018952:Antigens, CD34; D017239:Paclitaxel