title: The effect to IL-3Ralpha, downstream PI3k/Akt signaling of all-trans retinoic acid and arsenic trioxide in NB4 cells.
abstract: 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.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Juan-Ying
authors.initials: JY
authors.lastname: Wu
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Huang
authors.forename: Yuan-Zhong
authors.initials: YZ
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D053661:Interleukin-13 Receptor alpha1 Subunit / Q000096:biosynthesis / Q000502:physiology*; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis; D051058:Oncogene Protein v-akt / Q000187:drug effects*; D010087:Oxides / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; C508181:IL13RA1 protein, human; D053661:Interleukin-13 Receptor alpha1 Subunit; D009363:Neoplasm Proteins; D010087:Oxides; D012333:RNA, Messenger; D014212:Tretinoin; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt; D000077237:Arsenic Trioxide