title: Increased expression of amyloid precursor protein promotes proliferation and migration of AML1/ETO-positive leukemia cells and be inhibited by panobinostat.
abstract: Amyloid precursor protein (APP) is a highly conserved integral membrane protein extensively expressed in various types of cells. Previously we found that overexpression of APP in patients with AML1/ETO-positive acute myeloid leukemia (AML) associated with a higher incidence of extramedullary infiltrationin and indicate a poor prognosis. In this study, we attempted to define the roles of APP in AML1/ETO-positive leukemia cells. Western blotting and qRT-PCR analysis showed that protein levels of APP are significantly higher in Kasumi-1, a t(8;21)/ AML1/ETO-positive M2-type AML cell line. Stable knockdown of APP by lentivirus-based RNA interference (RNAi) dramatically impaired colony-formation and migration ability of Kasumi-1 cells, whereas APP knockdown had very little effect on cell viability, apoptosis, cell cycle and differentiation. We further explored whether the pan-histone deacetylase inhibitor panobinostat could deplete the protein levels of APP in Kasumi-1 cells. Treatment with panobinostat caused depletion of APP in Kasumi-1 cells. These findings indicate that overexpression of APP is involved in promoting proliferation and migration of AML1/ETO-positive leukemia cells and can be inhibited by panobinostat, which provide an attractive prospect for treatment of AML1/ETO-positive AML.
authors.forename: C L
authors.initials: CL
authors.lastname: Wang
authors.forename: B J
authors.initials: BJ
authors.lastname: Ding
authors.forename: L
authors.initials: L
authors.lastname: Jiang
authors.forename: C X
authors.initials: CX
authors.lastname: Yin
authors.forename: Q X
authors.initials: QX
authors.lastname: Zhong
authors.forename: G P
authors.initials: GP
authors.lastname: Yu
authors.forename: X D
authors.initials: XD
authors.lastname: Li
authors.forename: F Y
authors.initials: FY
authors.lastname: Meng
keywords: AML1/ETO; APP; Kasumi-1; panobinostat.