Combination of Pim kinase inhibitors and Bcl-2 antagonists in chronic lymphocytic leukemia cells.

ABSTRACT: The Pim proteins are Ser/Thr kinases over-expressed in several hematological malignancies such as chronic lymphocytic leukemia (CLL) and some solid cancers like prostate cancer. Several small molecules have been developed to inhibit these kinases. In prostate cancer cell lines, the Pim kinase inhibitor SMI-4a and the Bcl-2 antagonist ABT-737 resulted in synergistic cytotoxicity. Akin to prostate cancer cells, CLL lymphocytes over-express Pim and Bcl-2 proteins. It was hypothesized that similar cytotoxic interaction should be observed in CLL. This study evaluated the in vitro cytotoxic effect of three Pim kinase inhibitors (AZD1208, SGI-1776 and SMI-4a) combined with Bcl-2 antagonists (ABT-737 or ABT-199) in malignant CLL lymphocytes. Data indicated Pim kinase inhibitors in combination with

SUBMITTER: Cervantes-Gomez F 

PROVIDER: S-EPMC4814351 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature