We found that exposure of different CXCR4+ AML cell lines to T22-PE24-H6 nanoparticles in the low nanomolar range induces a potent cytotoxic effect mediated by apoptosis, as confirmed by its characteristic features, such as DNA condensation, apoptotic body formation, externalization of phosphatidylserine residues on the outer plasma membrane, as detected by Annexin V, caspase-3 activation, and PARP proteolysis in target cancer cells. Here, ANXA5 is linked to acute myeloid leukemia.