BACKGROUND Vitamin C suppresses leukaemogenesis by modulating Tet methylcytosine dioxygenase (TET) activity. However, its beneficial effect in the treatment of patients with acute myeloid leukaemia (AML) remains controversial. In this study, we aimed to identify a potential predictive biomarker for vitamin C treatment in AML. METHODS Gene expression patterns and their relevance to the survival of AML patients were analysed with The Cancer Genome Atlas (TCGA) and Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database cases. In vitro experiments were performed on AML cell lines, a SLC2A3-knockdown cell line and patient-derived primary AML cells. RESULTS SLC2A3 expression was significantly decreased in leukaemic blast cells. Below-median SLC2A3 expression was associated with poor overall survival. Low SLC2A3 expression was associated with less effective demethylation, and a diminished vitamin C effect in the AML and lymphoma cell lines. SLC2A3 knockdown in the KG-1 cell line decreased the response of vitamin C. In patient-derived primary AML cells, vitamin C only restored TET2 activity when SLC2A3 was expressed. CONCLUSION SLC2A3 could be used as a potential biomarker to predict the effect of vitamin C treatment in AML.

中文翻译：

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SLC2A3 介导的维生素 C 摄取减少促进白血病进展并阻碍 TET2 恢复。

背景维生素 C 通过调节 Tet 甲基胞嘧啶双加氧酶 (TET) 活性来抑制白血病发生。然而，其在治疗急性髓系白血病 (AML) 患者中的有益效果仍存在争议。在这项研究中，我们旨在确定一种潜在的预测性生物标志物，用于 AML 中的维生素 C 治疗。方法 使用癌症基因组图谱 (TCGA) 和治疗应用研究生成有效治疗 (TARGET) 数据库案例分析基因表达模式及其与 AML 患者生存的相关性。对 AML 细胞系、SLC2A3 敲低细胞系和患者来源的原代 AML 细胞进行了体外实验。结果白血病母细胞中SLC2A3的表达显着降低。低于中位数的 SLC2A3 表达与较差的总体生存率相关。SLC2A3 的低表达与去甲基化效果较差以及在 AML 和淋巴瘤细胞系中维生素 C 的作用减弱有关。KG-1 细胞系中的 SLC2A3 敲低降低了维生素 C 的反应。在患者来源的原代 AML 细胞中，维生素 C 仅在 SLC2A3 表达时恢复 TET2 活性。结论 SLC2A3 可作为潜在的生物标志物来预测维生素 C 治疗对 AML 的影响。