Nudix hydrolase (NUDT)15 is an important negative regulator of thiopurines. There are three types of thiopurines used clinically: azathioprine (a prodrug of mercaptopurine), mercaptopurine, and thioguanine. Variants in NUDT15 are associated with thiopurine-induced myelosuppression in patients with acute lymphoblastic leukemia (ALL) and those with inflammatory bowel diseases (IBD). NUDT15 poor metabolizer alleles are particularly prevalent in Asian and Hispanic ethnicities.1,2 A recent study shows variants in NUDT15 are associated with increased risk of thiopurine-induced myelosuppression among patients of European ancestry with IBD.3 Thiopurine Methyltransferase (TPMT) is another negative regulator of thiopurines activities. Patients with loss-of-function TPMT alleles are at higher risk for life-threatening myelosuppression than individual with wild-type alleles due to overexposure to active drug.4,5 The recently updated Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline recommends genotyping both TPMT and NUDT15 for thiopurines dosing.6
Click here for the full CPIC guideline for thiopurine dosing based on TPMT and NUDT15 genotypes.