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一名NUDT15缺乏症患者在开始使用硫嘌呤后出现严重骨髓抑制和脱发。

Severe myelosuppression and alopecia after thiopurine initiation in a patient with NUDT15 deficiency.

作者信息

Wu Annie Siyu, Mozessohn Lee, Kim Richard B, Zipursky Jonathan S

机构信息

Department of Medicine, University of Toronto, Toronto, Ontario, Canada.

Division of Medical Oncology/Hematology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.

出版信息

Br J Clin Pharmacol. 2025 May;91(5):1511-1515. doi: 10.1002/bcp.70047. Epub 2025 Mar 18.

Abstract

Thiopurines are a class of immunosuppressant and antineoplastic agents. They are widely used in the treatment of inflammatory bowel disease, haematological malignancies and autoimmune diseases, but can cause significant toxicity. Inherited gene mutations are now recognized as independent risk factors for severe adverse drug reactions to thiopurines even at 10-fold dose reductions. We present a case of thiopurine toxicity resulting in severe myelosuppression, hepatotoxicity and alopecia in an individual with homozygous *3/*3 loss-of-function alleles in the NUDT15 gene. Our case highlights important differences in gene mutation frequencies between races that can help guide pharmacogenomic testing.

摘要

硫嘌呤类药物是一类免疫抑制剂和抗肿瘤药物。它们被广泛用于治疗炎症性肠病、血液系统恶性肿瘤和自身免疫性疾病,但可能会引起严重毒性。即使将剂量降低10倍,遗传基因突变现在也被认为是硫嘌呤类药物严重药物不良反应的独立危险因素。我们报告了1例因硫嘌呤毒性导致严重骨髓抑制、肝毒性和脱发的病例,该患者NUDT15基因存在纯合*3/*3功能缺失等位基因。我们的病例突出了不同种族之间基因突变频率的重要差异,这有助于指导药物基因组学检测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc96/12035587/9f4e8f2944ba/BCP-91-1511-g001.jpg

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