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Impaired transport as a mechanism of resistance to thiopurines in human T-lymphoblastic leukemia cells
KI, Stockolm.
Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.ORCID iD: 0000-0002-2809-7591
Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
KI, Stockholm.
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
Abstract [en]

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.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-36780DOI: 10.1080/15257770600890848Local ID: 32533OAI: oai:DiVA.org:liu-36780DiVA: diva2:257629
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13

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Lindqvist Appell, MalinPeterson, Curt

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