As monotherapy, HDAC inhibitors are unlikely to impact the treatment of AML and advanced MDS although there is a strong biologic rationale for use of these agents in combination therapies. By inhibiting deacetylation of histones, HDAC inhibitors generate a more open chromatin structure more susceptible to the DNA damaging effects of anthracycline chemotherapeutic agents, in some instances when administered 48 hours after the HDAC inhibitor. In vitro, HDAC inhibitors potentiate the cytotoxic effects of anthracyclines in leukemia cell lines. Panobinostat, specifically, acts synergistically with the anthracycline doxorubicin to induce DNA damage, increase histone acetylation and activate programmed cell death in AML cell lines and primary AML cells. The administration of the anthracycline daunorubicin with panobinostat is predicted to be synergistic in vivo and may improve complete response and relapse rates for AML.