SIRT2 deacylase modulators control B cell metabolic reprogramming in EBV infection and mitogenic activation

SIRT2 modulation significantly alters gene expression and metabolism of EBV-infected B cells. Treatment with SIRT2 modulators drives hyperacetylation of targets involved in lipid metabolism, central carbon metabolism, and oxidative phosphorylation. EBV-positive and EBV-negative B cell lymphomas rely on glycolysis to avoid cell death after SIRT2 modulation, revealing a metabolic vulnerability that can be harnessed to kill lymphoma cells.

Overall, we have identified how SIRT2 could be implicated as a novel target of therapeutic potential for B cell lymphomas, while also defining fundamental roles for extranuclear lysine acetylation in regulating B cell proliferation and metabolism.