Meta-Biol

• Pathways

6-mercaptopurine (6MP) is used in the treatment of inflammatory diseases such as rheumatoid arthritis and childhood acute lymphoblastic leukemia. 6MP and its thioguanine nucleotide metabolites are principally inactivated by thiopurine methyltransferase (TPMT)-catalysed S-methylation. Defects in TPMT can cause thiopurine S-methyltransferase deficiency (TPMT deficiency; MIM:610460). Patients with intermediate or no TPMT activity are at risk of toxicity after receiving standard doses of thiopurine drugs. Inter-individual differences in response to these drugs are largely determined by genetic variation at the TPMT locus. Variants that cause complete or almost complete loss of function are A154T and Y240C (variants TPMT*3B and 3C, together called TPMT*3A), A80P (TPMT*2) and A167G (TPMT*23) (Szumlanski et al. 1996, Tai et al. 1997, Lindquist et al. 2007).