Thiopurine methyltransferase (TPMT) is a cytoplasmic transmethylase present in prokaryotes and eukaryotes, with high expression in human liver and kidney. It is an important enzyme in the phase II metabolic pathway, catalyzing the methylation of thiopurine drugs like azathioprine, 6-thioguanine, and 6-mercaptopurine, which are used to treat neoplasia, autoimmune diseases, and for transplant recipients [2].

In a combined heterozygous mouse model (Tpmt+/-/Nudt15+/-), excessive hematopoietic toxicity and metabolite (DNA-TG) accumulation were observed compared to wild-type or single heterozygous mice. This indicated that Tpmt, along with Nudt15, is crucial in thiopurine metabolism, and improper function of Tpmt can lead to adverse effects [1].

In conclusion, TPMT is vital for the metabolism of thiopurine drugs. Studies using the Tpmt/Nudt15 combined heterozygous mouse model have revealed its role in preventing excessive hematopoietic toxicity associated with thiopurine treatment, emphasizing its importance in personalized medicine for patients using these drugs.

References:

1. Maillard, Maud, Nishii, Rina, Yang, Wenjian, Haidar, Cyrine E, Yang, Jun J. . Additive effects of TPMT and NUDT15 on thiopurine toxicity in children with acute lymphoblastic leukemia across multiethnic populations. In Journal of the National Cancer Institute, 116, 702-710. doi:10.1093/jnci/djae004. https://pubmed.ncbi.nlm.nih.gov/38230823/

2. Katara, Pramod, Kuntal, Himani. 2015. TPMT Polymorphism: When Shield Becomes Weakness. In Interdisciplinary sciences, computational life sciences, 8, 150-155. doi:10.1007/s12539-015-0111-1. https://pubmed.ncbi.nlm.nih.gov/26297310/