To further interrogate the dependence of RNRi and ara‐C synergy upon catalytically active SAMHD1, we pre‐treated patient AML blasts ex vivo with virus‐like particles (VLPs) either containing (X) or lacking (dX) the lentiviral protein Vpx that depletes SAMHD1 by targeting it for proteasomal degradation, prior to incubating them with ara‐C and RNRi concentration–response matrices. This evidence concerns the gene SAMHD1 and acute myeloid leukemia.