组蛋白去乙酰化酶 4 的表达与儿童急性淋巴细胞白血病中泼尼松反应不良相关。

The expression of histone deacetylase 4 is associated with prednisone poor-response in childhood acute lymphoblastic leukemia.

机构信息

Jena University Hospital, Children's Clinic, Department of Pediatric Hematology and Oncology, Jena, Germany.

出版信息

Leuk Res. 2013 Oct;37(10):1200-7. doi: 10.1016/j.leukres.2013.07.016. Epub 2013 Aug 12.

DOI:10.1016/j.leukres.2013.07.016

Abstract

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.

摘要

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）同工型。在 93 例原发性 ALL 和 8 例健康供体样本中测定了 HDAC1-11 的表达。HDAC1、HDAC2 和 HDAC8 在 ALL 样本中的表达明显升高。HDAC 表达与临床病理参数的相关性分析表明，高 HDAC1、HDAC2、HDAC4 和 HDAC11 水平与不良预后因素显著相关。特别是，高 HDAC4 表达与初始白细胞计数高、T 细胞 ALL 和泼尼松反应不良相关。HDAC4 的 siRNA 介导抑制使 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 尤其是泼尼松反应不良患者的药物靶点。