RESUMEN
Our previous study has shown that CD9 knockdown could suppress cell proliferation, adhesion, migration and invasion, and promote apoptosis and the cytotoxicity of chemotherapeutic drugs in the Blineage acute lymphoblastic leukemia (BALL) cell line SUPB15. In this study, we further investigated the molecular mechanism underlying the effects of CD9 on leukemic cell progression and the efficacy of chemotherapeutic agents in BALL cells. Using the CD9knockdown SUPB15 cells, we demonstrated that the silencing of the CD9 gene significantly reduced the expression of phosphorylatedphosphatidylinositol3 kinase (pPI3K), phosphorylatedprotein kinase B (pAKT), Pglycoprotein (Pgp), multidrug resistanceassociated protein 1 (MRP1), breast cancer resistance protein (BCRP), matrix metalloproteinase 2 (MMP2) and phosphorylatedfocal adhesion kinase (pFAK). In addition, glutathione Stransferase (GST) pulldown assay showed the binding between CD9 and both PI3Kp85α and PI3Kp85ß in vitro, while coimmunoprecipitation assay showed the binding between CD9 and both PI3Kp85α and PI3Kp85ß in vivo. Furthermore, the PI3K/AKT inhibitor LY294002 mirrored the effects of CD9 knockdown in SUPB15 cells. Taken together, these findings demonstrated that CD9 activates the PI3K/AKT signaling pathway through direct interaction with PI3Kp85 in BALL cells. Our data provide evidence for the inhibition of the PI3K/AKT pathway as a novel therapeutic option in CD9 antigenpositive BALL.