Jianfeng Chen et al demonstrated that the PI3K-AKT-SOX2 axis exerts a pivotal role in the development of resistance to R-CHOP (combination of rituximab, cyclophospha-mide, doxorubicin, vincristine, and prednisone) treatment in diffuse large B-cell lymphoma (DLBCL) cells by impeding Ub-mediated SOX2 degradation and enhancing SOX2 stability, thereby preserving the stemness of drug-resistant DLBCL cells. Here, DDIT3 is linked to diffuse large B-cell lymphoma.