难治和复发性B细胞淋巴瘤往往受难以靶向的致癌基因MYC的驱动。在这里，我们报告了高MYC表达刺激增殖并在正常氧化应激水平下保护B淋巴瘤细胞免受凋亡的作用，而包括N-乙酰半胱氨酸（NAC）和维生素C（VitC）在内的化合物通过减少氧化应激诱导凋亡。NAC和VitC注射在高MYC表达的淋巴瘤细胞中有效减少肿瘤生长，但在低MYC表达的细胞中不起作用。MYC敲除使肿瘤对NAC和VitC具有耐药性，而MYC激活使B细胞对这些化合物敏感。机制上，NAC和VitC通过MYC的Cys117刺激MYC与EGR1的结合，将转录输出从细胞周期转移为凋亡基因表达。这些结果确定了一个红氧控制的机制，解释了MYC在维持增殖和防止凋亡中的作用，并为评估NAC或VitC在MYC驱动的B细胞淋巴瘤患者中的潜在治疗基础提供了理论依据。版权所有©2023 Elsevier Inc. 发布。

Refractory and relapsed B cell lymphomas are often driven by the difficult-to-target oncogene MYC. Here, we report that high MYC expression stimulates proliferation and protects B lymphoma cells from apoptosis under normal oxidative stress levels and that compounds including N-acetylcysteine (NAC) and vitamin C (VitC) induce apoptosis by reducing oxidative stress. NAC and VitC injections effectively reduce tumor growth in lymphoma cells with high MYC expression but not in those with low MYC expression. MYC knockdown confers tumor resistance to NAC and VitC, while MYC activation renders B cells sensitive to these compounds. Mechanistically, NAC and VitC stimulate MYC binding to EGR1 through Cys117 of MYC, shifting its transcriptional output from cell cycle to apoptosis gene expression. These results identify a redox-controlled mechanism for MYC's role in maintaining proliferation and preventing apoptosis, offering a potential therapeutic rationale for evaluating NAC or VitC in patients with MYC-driven B cell lymphoma.Copyright © 2023. Published by Elsevier Inc.