Vinblastine rapidly induces NOXA and acutely sensitizes primary chronic lymphocytic leukemia cells to ABT-737.

ABSTRACT: Proteins of the BCL2 family provide a survival mechanism in many human malignancies, including chronic lymphocytic leukemia (CLL). The BCL2 inhibitor ABT-263 (navitoclax) is active in clinical trials for lymphoid malignancies, yet resistance is expected on the basis of preclinical models. We recently showed that vinblastine can dramatically sensitize several leukemia cell lines to ABT-737 (the experimental congener of ABT-263). The goal of these experiments was to determine the impact of vinblastine on ABT-737 sensitivity in CLL cells isolated from peripheral blood and to define the underlying mechanism. Freshly isolated CLL cells from 35 patients, as well as normal lymphocytes and platelets, were incubated with various microtubule-disrupting agents plus ABT-737 to assess sensitivity to th

SUBMITTER: Bates DJ 

PROVIDER: S-EPMC3742582 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature