Synergistic and antagonistic AML cell type-specific responses to 5-AZA-2’-Deoxycytidine and 1-H-D-Arabinofuranosylcytosine

Abstract The search for synergistic drug combinations is critical to the treatment of drug-resistant cancer, such as acute myeloid leukemia (AML). Characterizing RNA expression associated with 5-aza-2'-deoxycytidine (DAC) and 1-h-D-arabinofuranosylcytosine (Ara-C) is a critical step to increase the efficacy of their combinatorial therapies. After 72 h of single-dose treatments of AML cells with DAC or Ara-C, the half-maximal effective concentration of DAC and Ara-C and the drug combination index were assessed. Pre-treatment with DAC restores cellular sensitivity in Ara-C-resistant AML cells. In contrast, DAC/Ara-C combinations are antagonistic in other Ara-C-sensitive AML cells. Our results provide an alternative approach for predicting what combinations, dosing and scheduling of drug delivery should be used to better individualize therapy of AML.