Association of Multiple Gene Polymorphisms Including Homozygous NUDT15 R139C With Thiopurine Intolerance During the Treatment of Acute Lymphoblastic Leukemia
Association of Multiple Gene Polymorphisms Including Homozygous NUDT15 R139C With Thiopurine Intolerance During the Treatment of Acute Lymphoblastic Leukemia
复制标题
包括纯合子 NUDT15 R139C 在内的多基因多态性与急性淋巴细胞白血病治疗期间硫嘌呤不耐受的关联
DOI：
10.1097/mph.0000000000002085
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Ito E
中科院分区：
文献类型：
--
作者：
Kudo K;Sato T;Takahashi Y;Yuzawa K;Kobayashi A;Kamio T;Sasaki S;Shimada J;Otani K;Tusjimoto S;Kato M;Toki T;Terui K;Ito E
虽然硫嘌呤是治疗急性淋巴细胞白血病的关键药物，但由于基因多态性，观察到不耐受的个体差异。一名患有b细胞前体急性淋巴细胞白血病的3岁男孩服用硫嘌呤后，由于长期血液毒性、慢性播散性念珠菌病和感染性心内膜炎引发多发性脑梗死，出现粘膜炎、败血症和噬血细胞性淋巴组织细胞增多症。该患者存在3个与硫嘌呤不耐受相关的基因多态性，包括纯合子NUDT15 R139C、杂合子ITPA C94A、纯合子MTHFR C677T和杂合子RFC1 G80A。因此，在发生意外不良反应时，应考虑由多基因多态性引起的不耐受的综合效应。
Although thiopurine is a crucial drug for treating acute lymphoblastic leukemia, individual variations in intolerance are observed due to gene polymorphisms. A 3-year-old boy with B-cell precursor acute lymphoblastic leukemia who was administered thiopurine developed mucositis, sepsis, and hemophagocytic lymphohistiocytosis due to prolonged hematologic toxicity, chronic disseminated candidiasis, and infective endocarditis that triggered multiple brain infarctions. The patient was found to harbor 3 gene polymorphisms associated with thiopurine intolerance including homozygous NUDT15 R139C, heterozygous ITPA C94A, and homozygous MTHFR C677T and heterozygous RFC1 G80A. Thus, the combined effect of intolerance via multiple gene polymorphisms should be considered in case of unexpected adverse reactions.