title: Genetic manipulation of drug sensitivity in haematopoietic cells.
abstract: The haematopoietic system can be manipulated genetically to increase either its resistance to drugs or its sensitivity to certain agents. Gene transfer and expression of specific drug-resistance factors might protect haematopoietic function during antitumour chemotherapy, or allow enrichment of gene-modified cells in vivo. By contrast, gene transfer of a prodrug activator, to confer sensitivity to otherwise nontoxic prodrugs, might allow deletion of engrafted cells in the event of an adverse effect such as graft-versus-host disease or the induction of a neoplasm. In addition, expression of a prodrug activator in tumour-infiltrating haematopoietic cells could provide a means of specifically activating a cytotoxic agent within a tumour mass.
authors.affiliation: Cancer Research UK Gene Therapy Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester, M20 4BX, UK. tsouthgate@picr.man.ac.uk
authors.forename: Thomas
authors.initials: T
authors.lastname: Southgate
authors.forename: Leslie J
authors.initials: LJ
authors.lastname: Fairbairn
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D019450:Genes, MDR; D041722:Genes, Transgenic, Suicide / Q000502:physiology; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods* / Q000639:trends; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D008954:Models, Biological; D015202:Protein Engineering / Q000379:methods; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes