Targeting metabolism and survival in chronic lymphocytic leukemia and Richter syndrome cells by a novel NF-κB inhibitor.

ABSTRACT: IT-901 is a novel and selective NF-κB inhibitor with promising activity in pre-clinical models. Here we show that treatment of chronic lymphocytic leukemia cells (CLL) with IT-901 effectively interrupts NF-κB transcriptional activity. CLL cells exposed to the drug display elevated mitochondrial reactive oxygen species, which damage mitochondria, limit oxidative phosphorylation and ATP production, and activate intrinsic apoptosis. Inhibition of NF-κB signaling in stromal and myeloid cells, both tumor-supportive elements, fails to induce apoptosis, but impairs NF-κB-driven expression of molecules involved in cell-cell contacts and immune responses, essential elements in creating a pro-leukemic niche. The consequence is that accessory cells do not protect CLL cells from IT-901-induced apoptos

SUBMITTER: Vaisitti T 

PROVIDER: S-EPMC5664392 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature