Combination of Pim kinase inhibitors with Bcl-2 antagonist in Chronic Lymphocytic Leukemia

In chronic lymphocytic leukemia (CLL), the intrinsic pathway, which leads to the death of normal lymphocytes, is blocked by overexpression of anti-apoptotic Bcl-2 family proteins and Pim kinases. Blocking both of these anti-apoptotic molecules should allow pro-apoptotic proteins to function normally, causing cancerous cells to die. ABT-737, a drug currently in clinical trials, antagonizes Bcl-2 but by itself does not induce considerable cell death. In this project, ABT-737 and a Pim kinase inhibitor were used in combination against isolated CLL cells. Although the combined agents induced greater CLL cell death than either alone, the effects were not additive or synergistic