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Abstract

Mechanisms of acquired resistance to three purine analogues, 2-chloro-2-deoxyadenosine (cladribine, CdA), 9-beta-D-arabinofuranosyl-2-fluoroadenine (fludarabine, Fara-A), and 2-chloro-2'-arabino-fluoro-2'-deoxyadenosine (clofarabine, CAFdA) were investigated in a human T-lymphoblastic leukemia cell line (CCRF-CEM). These analogues are pro-drugs and must be activated by deoxycytidine kinase (dCK). The CdA and CAFdA resistant cell lines exhibited increased resistance to the other nucleoside analogues activated by dCK. This was also the case for the Fara-A resistant cells, except that they were sensitive to CAFdA and guanosine analogues. The CdA and CANA resistant cells displayed a deficiency in dCK activity (to

Keywords

cladribine; clofarabine; fludarabine; ribonucleotide reductase; deoxycytidine kinase

Published in

Biochemical Pharmacology
2003, volume: 65, number: 2, pages: 237-247
Publisher: PERGAMON-ELSEVIER SCIENCE LTD

Publication identifier

  • DOI: https://doi.org/10.1016/S0006-2952(02)01484-3

Permanent link to this page (URI)

https://res.slu.se/id/publ/1790