Impaired transport as a mechanism of resistance to thiopurines in human T-lymphoblastic leukemia cells
2006 (English)In: Nucleosides, Nucleotides & Nucleic Acids, ISSN 1525-7770, E-ISSN 1532-2335, Vol. 25, no 9-11, 1039-1044 p.Article in journal (Refereed) Published
In order to better understand the mechanisms of resistance to thiopurines, we studied two sublines of the MOLT4 T-lymphoblastic leukemia cell line, resistant to 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG). We found that the underlying mechanism of resistance in both resistant cell lines was a markedly reduction in initial transport of 6-MP (3- and 5-fold, respectively, in 6-MP- and 6-TG-resistant cells). No significant alteration of activities of hypoxanthine-guanine phosphoribosyl transferase, thiopurine methyltransferase or inosine monophosphate dehydrogenase, the key enzymes involved in the metabolism of thiopurines was detected. We conclude that defected initial transport of thiopurines by cells may very well explain their resistance to these drugs. Copyright © Taylor & Francis Group, LLC.
Place, publisher, year, edition, pages
2006. Vol. 25, no 9-11, 1039-1044 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-36780DOI: 10.1080/15257770600890848Local ID: 32533OAI: oai:DiVA.org:liu-36780DiVA: diva2:257629