Here, we demonstrated for the first time to our knowledge that OLE, similarly to what we previously reported in neuroblastoma cells, acts as direct anti-tumor agent in B-ALL and with a lesser extent in AML cells, highlighting the potential molecular mechanisms involved, which are related to the induction of cellular stress and apoptosis, and are conceivably mediated by the extrinsic pathway, as witnessed by the highest modulation of TRAIL R1. This evidence concerns the gene TNFRSF10A and acute myeloid leukemia.