Decreased mitochondrial apoptotic priming underlies stroma-mediated treatment resistance in chronic lymphocytic leukemia.

ABSTRACT: Stroma induces treatment resistance in chronic lymphocytic leukemia (CLL), possibly because of alterations in the BCL-2 family of proteins, which are key regulators of apoptosis. We previously developed BH3 profiling, a functional assay that assesses mitochondrial depolarization in response to BH3-only peptides, to measure "apoptotic priming," the proximity of a cell to the apoptotic threshold. In the present study, we use BH3 profiling to show that CLL cells from the PB are highly primed. Increased priming is associated with improved clinical response and, unexpectedly, with unmutated IGHV status. Coculturing CLL cells in vitro with stroma decreases priming. Using matched PB, BM, and lymph node compartment samples, we found in vivo that BM-derived CLL cells are the least primed. CLL cells

SUBMITTER: Davids MS 

PROVIDER: S-EPMC3482860 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature