Distinct NF-kB Regulation Favors a Synergic Action of Pevonedistat and Laduviglusib in B-Chronic Lymphocytic Leukemia Cells Ex Vivo.

ABSTRACT: Background/Objectives: Chronic lymphocytic leukemia (CLL) remains an incurable B-cell malignancy. B-CLL cells exhibit an extended lifespan in part due to the activation of survival pathways such as NF-kB. A crosstalk between NF-kB and GSK-3β pathways has been reported. NF-kB has also been identified as a primary target of the NEDD8-activating enzyme inhibitor MLN4924. Our objective was to investigate potential synergies of MLN4924 with other NF-kB-targeting agents for the treatment of CLL and elucidate the mechanisms of action underlying this pathway regulation. Methods: To assess the cytotoxic efficacy of the combined ex vivo treatment with CHIR-99021 and MLN4924, we employed 7-AAD staining and XTT viability assays on primary samples from CLL patients. Subsequently, we condu

SUBMITTER: Arenas V 

PROVIDER: S-EPMC11816723 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature