title: The deacetylase inhibitor LAQ824 induces notch signalling in haematopoietic progenitor cells.
abstract: AML progenitor cells (AML-PC) undergo significant apoptosis in response to the deacetylase inhibitor (DACi) LAQ824 and lose the replating capacity which was not observed with the DACi valproic acid. Treatment of normal hematopoietic progenitor cells (HPC) with LAQ824 resulted in (i) inhibition of differentiation, (ii) an G2/M cell cycle arrest exclusively in multipotent CD34(+) HPC and (iii) induction of apoptosis predominantly in committed CD34(-) HPC. Gene expression analysis showed induction of coactivator and target genes of the notch pathway as well as cell cycle arrest-inducing genes in the most primitive CD34(+) CD38(-) HPC population which may in part be responsible for the considerable, but reversible haematotoxicity of this drug.
authors.affiliation: Department of Medicine II, Hematology and Oncology, Goethe Universität Frankfurt, Theodor-Stern-Kai 7, Frankfurt, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Schwarz
authors.forename: Annette
authors.initials: A
authors.lastname: Romanski
authors.forename: Elena
authors.initials: E
authors.lastname: Puccetti
authors.forename: Sarah
authors.initials: S
authors.lastname: Wietbrauk
authors.forename: Anja
authors.initials: A
authors.lastname: Vogel
authors.forename: Maren
authors.initials: M
authors.lastname: Keller
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Scott
authors.forename: Hubert
authors.initials: H
authors.lastname: Serve
authors.forename: Gesine
authors.initials: G
authors.lastname: Bug
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C477361:LAQ824; D051880:Receptors, Notch