Phosphorylation status and prognostic impacts of RSK2, PDPK1, and AKT in malignant lymphoma

Despite the oncogenic roles of the serine/threonine kinase PDPK1 and its key effectors, RSK2 and AKT, their activation status and prognostic significance remain unexamined in B cell lymphomas (BCLs). This study evaluated the phosphorylation states of PDPK1, the RSK2-N-terminal kinase domain (NTKD), and AKT through immunohistochemical analyses of 468 biopsied samples from patients with nine subtypes of MLs, including diffuse large B cell lymphoma (DLBCL) (n = 277) and follicular lymphoma (FL) (n = 121). PDPK1 was frequently phosphorylated in most subtypes, showing 98% in DLBCL and 76% in FL. RSK2-NTKD was phosphorylated in 100% and 69% of DLBCL and FL, respectively. AKT was phosphorylated in 68% and 53% of DLBCL and FL, respectively. Intriguingly, moderate to strong p-RSK2-NTKD expression significantly correlated with poor overall survival in DLBCL, especially in the non-GCB type, but not in FL. These emphasize the PDPK1/RSK2-NTKD pathway as a prognostic marker and a potential therapeutic target in various BCLs.