title: The role of epigenetics in the regulation of apoptosis in myelodysplastic syndromes and acute myeloid leukemia.
abstract: Disordered stem cell epigenetics and apoptosis-regulating mechanisms contribute essentially to the pathogenesis of myelodysplastic syndromes (MDS) and may trigger disease-progression to secondary acute myeloid leukemia (AML). Expression of apoptosis-mediators FAS (CD95) and DAPK1 the latter being also known for its association with autophagy are upregulated in neoplastic cells in patients with low-risk MDS and epigenetically silenced and downregulated in high-risk MDS and AML as confirmed by a study 50 MDS and 30 AMLs complementing this review. 5-Azacytidine (AZA) and 5-aza-2'deoxycytidine (DAC), promoted FAS and DAPK1 gene demethylation and their (re)expression as well as apoptosis in leukemic cell lines (HL-60, KG1) which can be reversed by siRNA against FAS. Thus, promoter-demethylation of FAS and DAPK1 represents a critical mechanism of drug-induced apoptosis in neoplastic cells in MDS and AML which underscores the clinical implication of epigenetically active therapies.
authors.affiliation: Ludwig Boltzmann Cluster Oncology, Vienna, Austria; Ludwig Boltzmann Institute for Leukemia Research and Hematology, Hanusch Hospital, Vienna, Austria. Electronic address: heidrun.karlic@meduniwien.ac.at.
authors.forename: Heidrun
authors.initials: H
authors.lastname: Karlic
authors.affiliation: Ludwig Boltzmann Cluster Oncology, Vienna, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Herrmann
authors.affiliation: Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling and 1st Medical Department, Hanusch Hospital, Vienna, Austria.
authors.forename: Franz
authors.initials: F
authors.lastname: Varga
authors.affiliation: Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling and 1st Medical Department, Hanusch Hospital, Vienna, Austria.
authors.forename: Roman
authors.initials: R
authors.lastname: Thaler
authors.affiliation: Ludwig Boltzmann Cluster Oncology, Vienna, Austria; Ludwig Boltzmann Institute for Leukemia Research and Hematology, Hanusch Hospital, Vienna, Austria.
authors.forename: Rene
authors.initials: R
authors.lastname: Reitermaier
authors.affiliation: Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling and 1st Medical Department, Hanusch Hospital, Vienna, Austria.
authors.forename: Silvia
authors.initials: S
authors.lastname: Spitzer
authors.affiliation: Department of Medicine I, Division of Hematology & Hemostaseology, Medical University of Vienna, Austria.
authors.forename: Viviane
authors.initials: V
authors.lastname: Ghanim
authors.affiliation: Ludwig Boltzmann Cluster Oncology, Vienna, Austria; Department of Medicine I, Division of Hematology & Hemostaseology, Medical University of Vienna, Austria.
authors.forename: Katharina
authors.initials: K
authors.lastname: Blatt
authors.affiliation: Ludwig Boltzmann Cluster Oncology, Vienna, Austria; Department of Medicine I, Division of Hematology & Hemostaseology, Medical University of Vienna, Austria.
authors.forename: Wolfgang R
authors.initials: WR
authors.lastname: Sperr
authors.affiliation: Ludwig Boltzmann Cluster Oncology, Vienna, Austria; Department of Medicine I, Division of Hematology & Hemostaseology, Medical University of Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Valent
authors.affiliation: Ludwig Boltzmann Cluster Oncology, Vienna, Austria; Ludwig Boltzmann Institute for Leukemia Research and Hematology, Hanusch Hospital, Vienna, Austria; 3rd Medical Department, Hanusch Hospital, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Pfeilstöcker
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics*
keywords: Apoptosis; Autophagy; Demethylating drugs; Epigenetics