High level of OPN expression effects on tumor genesis and cell protection from cytotoxic agents has been presented.11 Meanwhile, co-expression of OPN receptor CD44 with CD123 on CD34+/CD38- AML cells could confirm that OPN is a key regulator in LSCs.33 Various oncogene molecules, including PI3K/AKT, Wnt-β-catenin, and P70S6K/mTOR can be up-regulated by OPN that results in tumor growth or apoptosis inhibition as a cytoprotective action. 10, 34-37 Reciprocally, some oncogenes, including BCR-ABL-induced OPN over-expression via involving a number of signaling molecules such as PI-3K.38, 39. This evidence concerns the gene CD44 and acute myeloid leukemia.