Neutralization of B-Cell Activating Factor (BAFF) by Belimumab Reinforces Small Molecule Inhibitor Treatment in Chronic Lymphocytic Leukemia.

ABSTRACT: The introduction of idelalisib, ibrutinib and venetoclax for treatment of chronic lymphocytic leukemia (CLL) has greatly improved long term survival of patients. However, many patients do not achieve complete remission and suffer from development of resistance upon treatment with these small molecule inhibitors. Here we report that the TNF family member B-cell activating factor (BAFF) mediates resistance of CLL cells to idelalisib, ibrutinib and venetoclax by sustaining survival and preventing apoptosis of the malignant B cells as revealed by analysis of cellular ATP levels and mitochondrial membrane integrity as well as caspase activation, respectively. As BAFF also plays a prominent role in autoimmune diseases, the BAFF-neutralizing antibody belimumab was developed and approved for treat

SUBMITTER: Tandler C 

PROVIDER: S-EPMC7598196 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature