The expression of histone deacetylase 4 is associated with prednisone poor-response in childhood acute lymphoblastic leukemia
The expression of histone deacetylase 4 is associated with prednisone poor-response in childhood acute lymphoblastic leukemia
复制标题
DOI：
10.1016/j.leukres.2013.07.016
复制
发表时间：
2013-10-01
影响因子：
2.7
通讯作者：
Sonnemann, Juergen
中科院分区：
文献类型：
--
作者：
Gruhn, Bernd;Naumann, Thomas;Sonnemann, Juergen
本研究旨在鉴定与儿童急性淋巴细胞白血病（ALL）相关的组蛋白去乙酰化酶（HDAC）亚型。测定了93例原发性ALL和8例健康供体样本中HDAC1-11的表达。HDAC1、HDAC2和HDAC8在ALL样品中的表达明显升高。HDAC表达与临床病理参数的相关性分析显示，高水平的HDAC1、HDAC2、HDAC4和HDAC11与不良预后因素显著相关。特别是，高HDAC4表达与高初始白细胞计数、T细胞ALL和强的松不良反应相关。sirna介导的HDAC4抑制使T-ALL细胞系对依托泊苷诱导的细胞死亡敏感。总之，我们的数据表明HDAC4是儿童ALL的药物靶点，特别是在强的松反应不良的患者中。(C) 2013 Elsevier Ltd.版权所有。
This study aimed at the identification of histone deacetylase (HDAC) isoforms relevant for childhood acute lymphoblastic leukemia (ALL). Expression of HDAC1-11 was determined in 93 primary ALL and eight healthy donor samples. HDAC1, HDAC2 and HDAC8 showed significantly higher expressions in ALL samples. Correlation analysis of HDAC expression with clinicopathological parameters revealed that high HDAC1, HDAC2, HDAC4 and HDAC11 levels were significantly associated with unfavorable prognostic factors. Particularly, high HDAC4 expression was associated with high initial leukocyte count, T cell ALL and prednisone poor-response. siRNA-mediated inhibition of HDAC4 sensitized a T-ALL cell line to etoposide-induced cell death. In conclusion, our data point to HDAC4 as drug target in childhood ALL, especially in prednisone poor-responders. (C) 2013 Elsevier Ltd. All rights reserved.