Hepatotoxicity is a frequent complication during maintenance therapy of acute lymphoblastic leukemia (ALL) with 6-mercaptopurine and methotrexate. Elevated levels of methylated 6-mercaptopurine metabolites (MeMP) are associated with hepatotoxicity. However, not all mechanisms are known that lead to liver failure in patients with ALL. Variants in the POLG gene, which encodes the catalytic subunit of mitochondrial DNA polymerase gamma (POLG1), have been related to drug-induced hepatotoxicity, for example, by sodium valproate. The association of common POLG variants with hepatotoxicity during maintenance therapy was studied in 34 patients with childhood ALL. Of the screened POLG variants, four different variants were detected in 12 patients. One patient developed severe hepatotoxicity without elevated MeMP levels and harbored a heterozygous POLG p.G517V variant, which was not found in the other patients.

肝毒性是用 6-巯基嘌呤和甲氨蝶呤维持治疗急性淋巴细胞白血病 (ALL) 期间常见的并发症。甲基化 6-巯基嘌呤代谢物 (MeMP) 水平升高与肝毒性相关。然而，并非所有导致 ALL 患者肝功能衰竭的机制都是已知的。POLG基因编码线粒体 DNA 聚合酶 γ (POLG1) 的催化亚基，其变异与药物引起的肝毒性有关，例如丙戊酸钠引起的肝毒性。在 34 名儿童 ALL 患者中研究了维持治疗期间常见POLG变异与肝毒性的关联。在筛选的POLG变异中，在 12 名患者中检测到了 4 种不同的变异。一名患者出现严重肝毒性，但 MeMP 水平并未升高，并携带杂合 POLG p.G517V 变异，而其他患者中未发现这种变异。