Biochemical Pharmacology volume 77, issue 12, P1845-1853 2009 DOI: 10.1016/j.bcp.2009.03.006 View full text
Miha Milek, Natasa Karas Kuzelicki, Alenka Smid, Irena Mlinaric-Rascan

Abstract: Six-mercaptopurine (6-MP) is a pro-drug widely used in treatment of various diseases, including acute lymphoblastic leukaemia (ALL). Side-effects of thiopurine therapy have been correlated with thiopurine methyltransferase (TPMT) activity. We propose a novel TPMT-mediated mechanism of S-adenosylmethionine (SAM)-specific effects on 6-mercaptopurine (6-MP) induced cytotoxicity in a model cell line for acute lymphoblastic leukemia (MOLT). Our results show that exogenous SAM (10-50microM) rescues cells from the to…

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