The deacetylase inhibitor LAQ824 induces notch signalling in haematopoietic progenitor cells

被引：9
|
作者：
Schwarz, Kerstin [1 ]
Romanski, Annette [1 ]
Puccetti, Elena [2 ]
Wietbrauk, Sarah [1 ]
Vogel, Anja [1 ]
Keller, Maren [1 ]
Scott, Jeffrey W. [3 ]
Serve, Hubert [1 ]
Bug, Gesine [1 ]
机构：
[1] Goethe Univ Frankfurt, Dept Med Hematol & Oncol 2, Frankfurt, Germany
[2] Univ Marburg, Inst Mol Biol & Tumour Res, Marburg, Germany
[3] Novartis Pharmaceut, Florham Pk, NJ USA
来源：
LEUKEMIA RESEARCH | 2011年 / 35卷 / 01期
关键词：
Deacetylase inhibitor; Acute myeloid leukaemia; CD34(+) progenitor cells; Notch signalling; TRANS-RETINOIC ACID; VALPROIC ACID; SELF-RENEWAL; DIFFERENTIATION; LEUKEMIA; EXPRESSION; PROLIFERATION; MAINTAINS; COMPLEX; ETO;
D O I：
10.1016/j.leukres.2010.06.024
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
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. (C) 2010 Elsevier Ltd. All rights reserved.
引用
收藏
页码：119 / 125
页数：7
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