Retroviral transfer and expression of the human multiple drug resistance (MDR) gene in peripheral blood progenitor cells. 1996

M Ward, and P Pioli, and J Ayello, and R Reiss, and G Urzi, and C Richardson, and C Hesdorffer, and A Bank
Columbia University, College of Physicians and Surgeons, Department of Genetics and Development and Department of Medicine, New York, New York 10032, USA.

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.

UI MeSH Term Description Entries
D006412 Hematopoietic Stem Cells Progenitor cells from which all blood cells derived. They are found primarily in the bone marrow and also in small numbers in the peripheral blood. Colony-Forming Units, Hematopoietic,Progenitor Cells, Hematopoietic,Stem Cells, Hematopoietic,Hematopoietic Progenitor Cells,Cell, Hematopoietic Progenitor,Cell, Hematopoietic Stem,Cells, Hematopoietic Progenitor,Cells, Hematopoietic Stem,Colony Forming Units, Hematopoietic,Colony-Forming Unit, Hematopoietic,Hematopoietic Colony-Forming Unit,Hematopoietic Colony-Forming Units,Hematopoietic Progenitor Cell,Hematopoietic Stem Cell,Progenitor Cell, Hematopoietic,Stem Cell, Hematopoietic,Unit, Hematopoietic Colony-Forming,Units, Hematopoietic Colony-Forming
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012190 Retroviridae Family of RNA viruses that infects birds and mammals and encodes the enzyme reverse transcriptase. The family contains seven genera: DELTARETROVIRUS; LENTIVIRUS; RETROVIRUSES TYPE B, MAMMALIAN; ALPHARETROVIRUS; GAMMARETROVIRUS; RETROVIRUSES TYPE D; and SPUMAVIRUS. A key feature of retrovirus biology is the synthesis of a DNA copy of the genome which is integrated into cellular DNA. After integration it is sometimes not expressed but maintained in a latent state (PROVIRUSES). Leukemogenic Viruses,Leukoviruses,Oncornaviruses,Oncovirinae,Oncoviruses,Oncoviruses, Type C,RNA Tumor Viruses,Retroviruses,Type C Oncoviruses,C Oncovirus, Type,C Oncoviruses, Type,Leukemogenic Virus,Leukovirus,Oncornavirus,Oncovirus,Oncovirus, Type C,RNA Tumor Virus,Retrovirus,Tumor Virus, RNA,Tumor Viruses, RNA,Type C Oncovirus,Virus, Leukemogenic,Virus, RNA Tumor,Viruses, Leukemogenic,Viruses, RNA Tumor
D016133 Polymerase Chain Reaction In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. Anchored PCR,Inverse PCR,Nested PCR,PCR,Anchored Polymerase Chain Reaction,Inverse Polymerase Chain Reaction,Nested Polymerase Chain Reaction,PCR, Anchored,PCR, Inverse,PCR, Nested,Polymerase Chain Reactions,Reaction, Polymerase Chain,Reactions, Polymerase Chain
D017239 Paclitaxel A cyclodecane isolated from the bark of the Pacific yew tree, TAXUS BREVIFOLIA. It stabilizes MICROTUBULES in their polymerized form leading to cell death. 7-epi-Taxol,Anzatax,Bris Taxol,NSC-125973,Onxol,Paclitaxel, (4 alpha)-Isomer,Paxene,Praxel,Taxol,Taxol A,7 epi Taxol,NSC 125973,NSC125973,Taxol, Bris
D018014 Gene Transfer Techniques The introduction of functional (usually cloned) GENES into cells. A variety of techniques and naturally occurring processes are used for the gene transfer such as cell hybridization, LIPOSOMES or microcell-mediated gene transfer, ELECTROPORATION, chromosome-mediated gene transfer, TRANSFECTION, and GENETIC TRANSDUCTION. Gene transfer may result in genetically transformed cells and individual organisms. Gene Delivery Systems,Gene Transfer Technique,Transgenesis,Delivery System, Gene,Delivery Systems, Gene,Gene Delivery System,Technique, Gene Transfer,Techniques, Gene Transfer,Transfer Technique, Gene,Transfer Techniques, Gene
D018952 Antigens, CD34 Glycoproteins found on immature hematopoietic cells and endothelial cells. They are the only molecules to date whose expression within the blood system is restricted to a small number of progenitor cells in the bone marrow. CD34 Antigens,CD34 Antigen,Antigen, CD34
D019008 Drug Resistance, Neoplasm Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures. Antibiotic Resistance, Neoplasm,Antineoplastic Drug Resistance,Drug Resistance, Antineoplastic,Antineoplastic Agent Resistance,Neoplasm Drug Resistance,Resistance, Antineoplastic Agent,Resistance, Antineoplastic Drug
D020168 ATP Binding Cassette Transporter, Subfamily B, Member 1 A 170-kDa transmembrane glycoprotein from the superfamily of ATP-BINDING CASSETTE TRANSPORTERS. It serves as an ATP-dependent efflux pump for a variety of chemicals, including many ANTINEOPLASTIC AGENTS. Overexpression of this glycoprotein is associated with multidrug resistance (see DRUG RESISTANCE, MULTIPLE). ATP-Dependent Translocase ABCB1,MDR1 Protein,MDR1B Protein,Multidrug Resistance Protein 1,P-Glycoprotein,P-Glycoprotein 1,ABCB1 Protein,ATP Binding Cassette Transporter, Sub-Family B, Member 1,ATP-Binding Cassette, Sub-Family B, Member 1,CD243 Antigen,PGY-1 Protein,1, P-Glycoprotein,ABCB1, ATP-Dependent Translocase,ATP Dependent Translocase ABCB1,Antigen, CD243,P Glycoprotein,P Glycoprotein 1,PGY 1 Protein,Protein, MDR1B,Translocase ABCB1, ATP-Dependent

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