Thiopurine S-methyltransferase plays a pivotal role in thiopurine treatment outcomes. Here, we describe the effect of fluctuations in physiological levels of S-adenosyl-L-methionine (SAM) and related metabolites on TPMT activity levels in cell lines and erythrocytes from healthy donors. We determined higher TPMT activity in wild-type TPMT*1/*1 individuals with high SAM concentrations (n=96) compared to the low SAM level group (n=19; P(0.001). These findings confirm the results of our in vitro studies. The greatest effect of SAM-mediated TPMT stabilization was observed in the case of wild-type TPMT*1 and variant *3C allozymes. In addition to TPMT genotyping, SAM may serve as an important biochemical marker in individualization of thiopurine therapy.
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