• Corpus ID: 23986579

Retrovirally mediated gene transfer of Arg22 and Tyr22 forms of dihydrofolate reductase into the hematopoietic cell line K562: a comparison of methotrexate resistance.

  title={Retrovirally mediated gene transfer of Arg22 and Tyr22 forms of dihydrofolate reductase into the hematopoietic cell line K562: a comparison of methotrexate resistance.},
  author={Stephen E Braun and R. Scott McIvor and A. Davidson and Mazen Hanna and C. M. Traycoff and D A Berebetsky and Ren{\'e} Gonin and Hal E. Broxmeyer and Kenneth Cornetta},
  journal={Cancer gene therapy},
  volume={4 1},
Mutations in the enzyme dihydrofolate reductase (DHFR) can confer resistance to the inhibitory effects of folate analogs such as methotrexate (Mtx) and trimetrexate (Ttx). Retroviral vectors expressing the DHFR-Arg22 mutants and the newly described DHFR-Tyr22 mutant were used to transduce the hematopoietic cell line K562. In vitro selection of vector-containing cells was documented via polymerase chain reaction and Southern analysis. When proliferation of selected vector-containing cells was… 
Maintenance of differential methotrexate toxicity between cells expressing drug-resistant and wild-type dihydrofolate reductase activities in the presence of nucleosides through nucleoside transport inhibition.
It is concluded that nucleoside transport inhibition increases the toxicity and selectivity of MTX in cultured cells, and therefore is an effective way to maintain differential MTX toxicity between unmodified and DHFR-modified cells.
Gene therapy for chronic myelogenous leukemia (CML): a retroviral vector that renders hematopoietic progenitors methotrexate-resistant and CML progenitors functionally normal and nontumorigenic in vivo
The tyr22-DHFR gene in the LasBD vector can protect normal hematopoietic cells from MTX-mediated toxicity, whereas the AS sequences in LasBD can suppress expression of the BCR/ABL gene and restore normal function of BCR-ABL cDNA-containing cells.
Retroviral gene therapy in hematopoietic diseases
This review will limit the discussion to three areas of active research: the treatment of genetic diseases, the use of drug resistance gene vectors in autologous transplantation, and tumor immunization strategies in cancer.
Chronic myelogenous leukaemia CD34+ cells exit G0/G1 phases of cell cycle more rapidly than normal marrow CD34+ cells
Data suggest that enhanced cell cycle activation of CML CD34+ cells, by either autocrine stimuli or via enhanced sensitivity to exogenous stimuli, may be partially responsible for the pronounced cellular expansion characteristic of C ML.
Cancer gene therapy: an awkward adolescence
Some of the ancillary benefits of research on cancer gene therapy, including the development of public-private partnerships, recruitment of laboratory scientists into clinical research, and credentialing of potential cancer cell targets for therapies other than gene therapy are noted.