MYST2 acetyltransferase expression and Histone H4 Lysine acetylation are suppressed in AML

Tim Sauer; Maria Francisca Arteaga; Fabienne Isken; Christian Rohde; Katja Hebestreit; Jan-Henrik Mikesch; Matthias Stelljes; Chunhong Cui; Fengbiao Zhou; Stefanie Göllner; Nicole Bäumer; Gabriele Köhler; Utz Krug; Christian Thiede; Gerhard Ehninger; Bayram Edemir; Peter Schlenke; Wolfgang E Berdel; Martin Dugas; Carsten Müller-Tidow

doi:10.1016/j.exphem.2015.05.010

MYST2 acetyltransferase expression and Histone H4 Lysine acetylation are suppressed in AML

Exp Hematol. 2015 Sep;43(9):794-802.e4. doi: 10.1016/j.exphem.2015.05.010. Epub 2015 Jun 11.

Authors

Tim Sauer¹, Maria Francisca Arteaga¹, Fabienne Isken¹, Christian Rohde², Katja Hebestreit³, Jan-Henrik Mikesch¹, Matthias Stelljes¹, Chunhong Cui², Fengbiao Zhou², Stefanie Göllner², Nicole Bäumer¹, Gabriele Köhler⁴, Utz Krug¹, Christian Thiede⁵, Gerhard Ehninger⁵, Bayram Edemir², Peter Schlenke⁶, Wolfgang E Berdel¹, Martin Dugas³, Carsten Müller-Tidow⁷

Affiliations

¹ Department of Medicine A, Hematology, Hemostaseology, Oncology and Pneumology, University of Muenster, Muenster, Germany.
² Department of Medicine, Hematology and Oncology, University of Halle, Halle, Germany.
³ Institute of Medical Informatics, University of Muenster, Muenster, Germany.
⁴ Gerhard-Domagk Institute of Pathology, University of Muenster, Muenster, Germany.
⁵ Department of Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany.
⁶ Institute of Transfusion Medicine, University of Muenster, Muenster, Germany.
⁷ 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: [email protected].

PMID: 26072331
DOI: 10.1016/j.exphem.2015.05.010

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylation
Animals
Cell Survival
Gene Expression Regulation, Enzymologic*
Gene Expression Regulation, Leukemic*
Histone Acetyltransferases / biosynthesis*
Histone Acetyltransferases / genetics
Histones / genetics
Histones / metabolism*
Humans
Leukemia, Myeloid, Acute / genetics
Leukemia, Myeloid, Acute / metabolism*
Leukemia, Myeloid, Acute / mortality
Leukemia, Myeloid, Acute / pathology
Mice
Tumor Suppressor Proteins / biosynthesis*
Tumor Suppressor Proteins / genetics

Substances

Histones
Tumor Suppressor Proteins
Histone Acetyltransferases
KAT7 protein, human
Kat7 protein, mouse