title: MYST2 acetyltransferase expression and Histone H4 Lysine acetylation are suppressed in AML.
abstract: Chromatin-modifying enzymes are frequently altered in acute myeloid leukemia (AML). In the current study, we identified MYST2, a core histone acetyltransferase, to be suppressed in blast cells from AML patients compared with nonmalignant hematopoietic progenitor cells. Functionally, loss of MYST2 accelerated leukemic growth and colony formation, while forced expression of MYST2 induced H4K5 acetylation (H4K5Ac) and suppressed hematopoietic progenitor cell growth. Consistently, global H4K5Ac levels were frequently decreased in AML blasts. Low levels of H4K5Ac were most prominent in patients with complex karyotype AML and were associated with inferior overall survival in univariate but not multivariate analysis. ChIP-seq experiments in primary AML patients' blasts revealed widespread H4K5Ac deregulation, most prominent at gene promoters. Taken together, MYST2 is a repressed growth suppressor in AML mediating reduced acetylation of histone 4 at residue 5 and is associated with inferior AML patient survival.
authors.affiliation: Department of Medicine A, Hematology, Hemostaseology, Oncology and Pneumology, University of Muenster, Muenster, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Sauer
authors.affiliation: Department of Medicine A, Hematology, Hemostaseology, Oncology and Pneumology, University of Muenster, Muenster, Germany.
authors.forename: Maria Francisca
authors.initials: MF
authors.lastname: Arteaga
authors.affiliation: Department of Medicine A, Hematology, Hemostaseology, Oncology and Pneumology, University of Muenster, Muenster, Germany.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Isken
authors.affiliation: Department of Medicine, Hematology and Oncology, University of Halle, Halle, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Rohde
authors.affiliation: Institute of Medical Informatics, University of Muenster, Muenster, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Hebestreit
authors.affiliation: Department of Medicine A, Hematology, Hemostaseology, Oncology and Pneumology, University of Muenster, Muenster, Germany.
authors.forename: Jan-Henrik
authors.initials: JH
authors.lastname: Mikesch
authors.affiliation: Department of Medicine A, Hematology, Hemostaseology, Oncology and Pneumology, University of Muenster, Muenster, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Stelljes
authors.affiliation: Department of Medicine, Hematology and Oncology, University of Halle, Halle, Germany.
authors.forename: Chunhong
authors.initials: C
authors.lastname: Cui
authors.affiliation: Department of Medicine, Hematology and Oncology, University of Halle, Halle, Germany.
authors.forename: Fengbiao
authors.initials: F
authors.lastname: Zhou
authors.affiliation: Department of Medicine, Hematology and Oncology, University of Halle, Halle, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Göllner
authors.affiliation: Department of Medicine A, Hematology, Hemostaseology, Oncology and Pneumology, University of Muenster, Muenster, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Bäumer
authors.affiliation: Gerhard-Domagk Institute of Pathology, University of Muenster, Muenster, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Köhler
authors.affiliation: Department of Medicine A, Hematology, Hemostaseology, Oncology and Pneumology, University of Muenster, Muenster, Germany.
authors.forename: Utz
authors.initials: U
authors.lastname: Krug
authors.affiliation: Department of Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Thiede
authors.affiliation: Department of Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Ehninger
authors.affiliation: Department of Medicine, Hematology and Oncology, University of Halle, Halle, Germany.
authors.forename: Bayram
authors.initials: B
authors.lastname: Edemir
authors.affiliation: Institute of Transfusion Medicine, University of Muenster, Muenster, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Schlenke
authors.affiliation: Department of Medicine A, Hematology, Hemostaseology, Oncology and Pneumology, University of Muenster, Muenster, Germany.
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Berdel
authors.affiliation: Institute of Medical Informatics, University of Muenster, Muenster, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Dugas
authors.affiliation: Department of Medicine A, Hematology, Hemostaseology, Oncology and Pneumology, University of Muenster, Muenster, Germany; Department of Medicine, Hematology and Oncology, University of Halle, Halle, Germany. Electronic address: Carsten.Mueller-Tidow@UK-Halle.de.
authors.forename: Carsten
authors.initials: C
authors.lastname: Müller-Tidow
mesh_terms: D000107:Acetylation; D000818:Animals; D002470:Cell Survival; D015971:Gene Expression Regulation, Enzymologic; D015973:Gene Expression Regulation, Leukemic; D051548:Histone Acetyltransferases / Q000096:biosynthesis* / Q000235:genetics; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D051379:Mice; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D006657:Histones; D025521:Tumor Suppressor Proteins; D051548:Histone Acetyltransferases; C496553:KAT7 protein, human; C525638:Kat7 protein, mouse