ABCMdb

PMID: 16211086

Zaboikin M, Srinivasakumar N, Schuening F
Gene therapy with drug resistance genes.
Cancer Gene Ther. 2006 Apr;13(4):335-45., [PubMed]

Sentences

No. Mutations Sentence Comment

71 ABCB1 p.Gly185Val In a recent study Modlich et al.62 demonstrated that leukemogenesis in mice transplanted with marrow mononuclear cells transduced with MDR1 containing retroviral vector correlated with increased number of vector integration sites in Table 1 Transgenes commonly used for in vivo selection of transduced cells Transgene Mutants useful for in vivo selection Mechanism of action Selection agents Advantages Disadvantages DHFR L22Y F31S Provides resistance to antifolates Methotrexate Trimetrexate K Provides high levels of chemoprotection K Relative lack of toxicity from antifolate drugs K Drugs used for selection are not genotoxica K Works on S-phase cells only MDR1 Wild type Membrane pump extrudes drugs Colchicine Actinomycin D Etoposide Taxol Vinblastine K Provides high levels of protection K Cryptic splice sites make transgene unstable in viral vectors K Expressed at high levels in hematopoietic cells K Possible myeloproliferative effect on transduced cells G185V K Drugs used for selection are genotoxica MGMT P140K P140A G156A Removes alkyl groups from the O6 position of guanine and thymidine BCNU TMZ ACNU Dacarbazine Procarbazine K Expressed at low levels in stem cells K Modest levels of chemoprotection K Drugs used for selection are genotoxica GST-pi Wild type Inactivates drugs by conjugating glutathione Adriamycin Cisplatin Cyclophosphamide Melphalan K Provides resistance to different spectrum of drugs K May be useful for improving the effectiveness of other in vivo selection markers (e.g. MRP1) K Provides rather low levels of protection K Drugs used for selection are genotoxica BCNU: 1,3-bis(2-chloroethyl)-1-nitrosourea; TMZ: Temozolomide; ACNU: Chloroethylnitrosourea. Login to comment