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CEM cell lines genetically deficient in either nucleoside transport or deoxycytidine kinase activity

 

OHSU # 1626

Summary:

Technology Overview:

Two nucleoside transport-deficient cell lines were developed through isolation from a hypoxanthine-guanine phosphoribosyltransferase-deficient derivative of wild type CEM cells (a human T lymphoblast cell line originally derived from a patient with acute lymphocytic leukemia). The Ara-C/8C and TUB-4D clones were isolated by virtue of their resistance to 8 µM arabinosylcytosine and 4µM tubercidin, respectively. One cell line completely deficient in deoxycytidine kinase activity, the Ara-C/8D clone, is a clonal derivative of an hypoxanthine-guanine phosphoribosyltransferase-deficient parent CEM cell line originally isolated in semi-solid agarose containing 8µM arabinosylcytosine. The Ara-C/8C and TUB-4D cell lines are cross-resistant to a spectrum of cytotoxic nucleosides to which parental and Ara-C/8D cell are sensitive.

Cytarabine (Ara-C), a pyrimidine analog, is a conventional anti-cancer chemotherapeutic commonly used for the treatment of acute myeloid leukemia. Although Ara-C treatment often induces partial or complete remission of cancerous tissue, many patients eventually develop resistance. Ara-C/8C cells demonstrate cross-resistance to gemcitabine and 2’, 3’-dideoxycytidine. Therefore, this cell line may be useful for research into nucleoside transport deficiencies as well as anti-cancer chemotherapeutic analysis.

The Arac-C/8D cell line has been studied in detail for some time and found to express negligible deoxycytidine kinase activity and increased resistance to 2’-deoxyadenosine and 2’-deoxyguanosine-induced cytotoxicity as well as marked resistance to dideoxycytidine. The Ara-C/8D cell line has been found to contain two DNA mutations within the 2’-deoxycytidein kinase gene conferring its resistance.

Links/Publications: Ulllman et al., J Biol Chem. 1988 Sep 5;263(25):12391-6. Owens et al., Cancer Res. 1992 May 1;52(9):2389-93.

Licensing Opportunity: The cell lines are available for non-exclusive licensing.

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503-494-9839