Cap-Translation Inhibitor, 4EGI-1, Restores Sensitivity to ABT-737 Apoptosis through Cap-Dependent and -Independent Mechanisms in Chronic Lymphocytic Leukemia

Abstract

Overall protein synthesis and cap-complex formation are induced by microenvironment stimuli in CLL. Inhibition of the cap-complex was not sufficient to repress BCL2 family prosurvival expression, but 4EGI-1 inhibited BCL2A1 and BCL2L1 while inducing NOXA through cap-dependent and -independent mechanisms. 4EGI-1 and ABT-737 synergized to produce apoptosis, and these agents may be the basis for a therapeutically useful combination.