“…NUDT15 dephosphorylates thiopurine active metabolites and reduces the formation of active 6TG nucleotides, whereas ITPA is assumed to stimulate the formation of 6TG nucleotides. Results with respect to the influence of ITPA polymorphism in relation to myelosuppression, hepatotoxicity or TGN formation have not been consistent and its clinical relevance is still controversial ( Gerbek et al., 2018 ; Milosevic et al., 2018 ; Soler et al., 2018 ; Zhou et al., 2018 ; Khera et al., 2019 ; Wahlund et al., 2020 ). In contrast, in many recent studies, NUDT15 gene defects (rs116855232, rs186364861, rs869320766, rs201094029) have shown to result in increased TG availability for incorporation into DNA and have consistently been associated with TG toxicity including early myelosuppression ( Chiengthong et al., 2016 ; Moriyama et al., 2016 ; Lee and Yang, 2017 ; Moriyama et al., 2017 ; Moriyama et al., 2017 ; Soler et al., 2018 ; Choi et al., 2019 ; Khera et al., 2019 ; Koutsilieri et al., 2019 ).…”