Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
Br J Cancer. 2020 May;122(10):1445-1452. doi: 10.1038/s41416-020-0788-8. Epub 2020 Mar 16.
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.
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.
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.
SLC2A3 could be used as a potential biomarker to predict the effect of vitamin C treatment in AML.
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）患者中的有益作用仍存在争议。在这项研究中，我们旨在确定维生素 C 治疗 AML 的潜在预测生物标志物。
利用癌症基因组图谱（TCGA）和治疗性应用研究以产生有效治疗方法（TARGET）数据库中的病例，分析基因表达模式及其与 AML 患者生存的相关性。在 AML 细胞系、SLC2A3 敲低细胞系和患者来源的原发性 AML 细胞中进行了体外实验。
SLC2A3 在白血病原始细胞中的表达显著降低。低于中位数的 SLC2A3 表达与总生存期不良相关。低 SLC2A3 表达与去甲基化效果较差以及 AML 和淋巴瘤细胞系中维生素 C 作用减弱相关。在 KG-1 细胞系中敲低 SLC2A3 会降低维生素 C 的反应。在患者来源的原发性 AML 细胞中，只有在表达 SLC2A3 时，维生素 C 才能恢复 TET2 活性。
SLC2A3 可作为预测 AML 患者维生素 C 治疗效果的潜在生物标志物。
