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

被引：26

作者：

Sauer, Tim ^{[1
]}

Arteaga, Maria Francisca ^{[1
]}

Isken, Fabienne ^{[1
]}

Rohde, Christian ^{[2
]}

Hebestreit, Katja ^{[3
]}

Mikesch, Jan-Henrik ^{[1
]}

Stelljes, Matthias ^{[1
]}

Cui, Chunhong ^{[2
]}

Zhou, Fengbiao ^{[2
]}

Goellner, Stefanie ^{[2
]}

Baeumer, Nicole ^{[1
]}

Koehler, Gabriele ^{[4
]}

Krug, Utz ^{[1
]}

Thiede, Christian ^{[5
]}

Ehninger, Gerhard ^{[5
]}

Edemir, Bayram ^{[2
]}

Schlenke, Peter ^{[6
]}

Berdel, Wolfgang E. ^{[1
]}

Dugas, Martin ^{[3
]}

Mueller-Tidow, Carsten ^{[1
,2
]}

机构：

[1] Univ Munster, Dept Med A, Hematol Hemostaseol Oncol & Pneumol, D-48149 Munster, Germany

[2] Univ Halle, Dept Med Hematol & Oncol, D-06120 Halle, Germany

[3] Univ Munster, Inst Med Informat, D-48149 Munster, Germany

[4] Univ Munster, Gerhard Domagk Inst Pathol, D-48149 Munster, Germany

[5] Univ Hosp Carl Gustav Carus, Dept Med 1, Dresden, Germany

[6] Univ Munster, Inst Transfus Med, D-48149 Munster, Germany

来源：

EXPERIMENTAL HEMATOLOGY | 2015年 / 43卷 / 09期

关键词：

ACUTE MYELOID-LEUKEMIA; TUMOR-SUPPRESSOR; MUTATIONS; REGULATORS; JADE-1; SYSTEM; FAMILY; ADULTS; GENES; ALPHA;

D O I：

10.1016/j.exphem.2015.05.010

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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. Copyright (C) 2015 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc.

引用

页码：794 / 802

页数：9

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