Efficacy of panobinostat and marizomib in acute myeloid leukemia and bortezomib-resistant models

• Panobinostat elicits cell death in acute myeloid leukemia (AML) cell lines.
• Cell lines resistant to proteasome inhibitors are sensitive to panobinostat.
• Synergy is observed with panobinostat and proteasome inhibitors in AML lines.

Current relapse rates in acute myeloid leukemia (AML) highlight the need for new therapeutic strategies. Panobinostat, a novel pan-histone deacetylase inhibitor, and marizomib, a second-generation proteasome inhibitor, are emerging as valuable therapeutic options for hematological malignancies. Here we evaluated apoptotic effects of this combinatorial therapy in AML models and report earlier and higher reactive oxygen species induction and caspase-3 activation and greater caspase-8 dependence than with other combinations. In a bortezomib refractory setting, panobinostat induced high levels of DNA fragmentation, and its action was significantly augmented when combined with marizomib. These data support further study of this combination in hematological malignancies.