The effect to IL-3Ralpha, downstream PI3k/Akt signaling of all-trans retinoic acid and arsenic trioxide in NB4 cells.

All-trans retinoic acid (ATRA) and arsenic trioxide (As2O3) are the classic drugs used for induction therapy of acute promyelocytic leukemia (APL). IL-3Ralpha (CD123) is a specific marker of acute myeloid leukemia stem cells (AML-LSCs). The over-expression of IL-3Ralpha in patients with AML is related to high white blood cells counts, high percentages of blast cells, and poor prognosis. Moreover, in some studies, IL-3Ralpha has been considered a new detection marker of minimal residual disease in the bone marrow from patients with APL. In contrast to ATRA, As2O3 reduces both mRNA and protein expression of IL-3Ralpha and inhibits the activity of PI3K/Akt after 24 h, 48 h, and 72 h of exposure. Furthermore, NB4 cells adhered to the human stroma cell line HS-5 cells were used as an in vitro model of APL cells in the bone marrow microenvironment. Our results demonstrate that adhesion to HS-5 cells up-regulated IL-3Ralpha protein expression and activated the downstream PI3K/Akt signaling pathway in NB4 cells. Compared with ATRA, As2O3 more potently inhibits proliferation of NB4 cells adhered to stroma cells.