A MYC-controlled redox switch protects B lymphoma cells from EGR1-dependent apoptosis

Haidong Yao; Xue Chen; Ting Wang; Muhammad Kashif; Xi Qiao; Elin Tüksammel; Lars-Gunnar Larsson; Sam Okret; Volkan I Sayin; Hong Qian; Martin O Bergo

doi:10.1016/j.celrep.2023.112961

A MYC-controlled redox switch protects B lymphoma cells from EGR1-dependent apoptosis

Cell Rep. 2023 Aug 29;42(8):112961. doi: 10.1016/j.celrep.2023.112961. Epub 2023 Aug 9.

Authors

Affiliations

¹ Department of Biosciences and Nutrition, Karolinska Institutet, 141 83 Huddinge, Sweden.
² Department of Biosciences and Nutrition, Karolinska Institutet, 141 83 Huddinge, Sweden; Department of Plastic and Cosmetic Surgery, TongJi Hospital, TongJi Medical College, Huazhong University of Science and Technology, Wuhan 430 030, China.
³ Center for Hematology and Regenerative Medicine, Department of Medicine Huddinge, Karolinska University Hospital, 141 86 Huddinge, Sweden.
⁴ Department of Microbiology, Tumor and Cell Biology (MTC), Biomedicum, Karolinska Institutet, Solnavägen 9, Stockholm SE-171 65, Sweden.
⁵ Sahlgrenska Center for Cancer Research, Department of Surgery, Institute of Clinical Sciences, University of Gothenburg, 405 30 Gothenburg, Sweden; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, 405 30 Gothenburg, Sweden.
⁶ Center for Hematology and Regenerative Medicine, Department of Medicine Huddinge, Karolinska University Hospital, 141 86 Huddinge, Sweden. Electronic address: hong.qian@ki.se.
⁷ Department of Biosciences and Nutrition, Karolinska Institutet, 141 83 Huddinge, Sweden. Electronic address: martin.bergo@ki.se.

PMID: 37561633
DOI: 10.1016/j.celrep.2023.112961

Abstract

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.

Keywords: B cell; CP: Cancer; MYC; apoptosis; lymphoma; vitamin C.