The enzymes encoded by thiopurine s-methyltransferase (TPMT) and nudix hydrolase 15 (NUDT15) play a key role in the metabolic pathway of thiopurines as they modulate drug activation and limit the accumulation of toxic metabolites: TPMT can methylate 6-MP into the inactive metabolite 6-MMP or 6-TIMP, resulting in the active metabolite 6-TGNs, responsible for hepatotoxicity associated with thiopurines; NUDT15 hydrolyzes and inactivates the 6-TGNs and is associated with thiopurine-induced leukopenia. This evidence concerns the gene NUDT15 and Decreased total leukocyte count.