Expression of histone deacetylases in diffuse large B-cell lymphoma and its clinical significance.
Expression of histone deacetylases in diffuse large B-cell lymphoma and its clinical significance.
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DOI：
10.7150/ijms.8522
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发表时间：
2014
影响因子：
3.6
通讯作者：
Yoo J
中科院分区：
文献类型：
--
作者：
Lee SH;Yoo C;Im S;Jung JH;Choi HJ;Yoo J
背景：组蛋白去乙酰化酶抑制剂是一类用于治疗恶性肿瘤的新药。弥漫性大B细胞淋巴瘤（DLBCL）是最常见的B细胞淋巴瘤类型，占所有B细胞淋巴瘤的40%以上。在这项研究中，我们的目的是确定组蛋白去乙酰化酶（HDAC）在DLBCL的表达模式，检查HDAC表达模式是否不同的情况下，并评估这些结果是否有临床意义。材料和方法：我们选择了2001-2012年在韩国天主教大学圣文森特医院诊断的91例DLBCL病例。我们进行了病理切片检查，并收集了临床数据，包括年龄，性别，肿瘤部位，生存时间和死亡率。使用HDAC的一抗进行免疫组织化学分析，包括I类HDAC 1和2、IIa类HDAC 4和5以及IIb类HDAC 6。确定表达位点为细胞核、细胞质或两者。染色强度分为低和高。我们评估了HDAC表达水平与临床数据和生存分析之间的相关性。结果：91例患者中，男性46例（50.5%），女性45例（49.5%）。以老年人居多，46岁以上74例（81.3%）。46例（50.5%）有淋巴结转移，45例（49.5%）有淋巴结转移。在淋巴结淋巴瘤中，HDAC 2染色强阳性，而HDAC 4染色弱或阴性;然而，与生存率无显著相关性。但HDAC 2核高表达的淋巴结淋巴瘤和HDAC 2核高表达而HDAC 4核低表达的淋巴结淋巴瘤患者的生存期明显短于其他病例。结论：HDAC 2核表达增高可能在DLBCL患者的生存中起重要作用，尤其是在淋巴结淋巴瘤患者中，这与较短的生存时间相关。我们的研究结果可能对通过表观遗传调控治疗DLBCL具有重要意义。
Background: Histone deacetylase inhibitors are a new class of drugs used in treatment of malignant tumors. Diffuse large B-cell lymphoma (DLBCL) is the most common type of B-cell lymphoma, and it accounts for more than 40% of all B-cell lymphomas. In this study, we aimed to determine the expression patterns of histone deacetylases (HDACs) in DLBCL, to examine whether HDAC expression patterns differ among cases, and to assess whether these findings have clinical significance. Materials and methods: We selected 91 cases of DLBCL diagnosed at St. Vincent Hospital, The Catholic University of Korea, from 2001-2012. We performed a pathology slide review and collected clinical data including age, sex, tumor site, survival time, and mortality. Immunohistochemical analysis was performed using primary antibodies for HDACs, including HDAC1 and 2 of class I, HDAC4 and 5 of class IIa, and HDAC6 of class IIb. Expression site was determined to be nuclear, cytoplasmic, or both. Staining intensities were graded as low and high. We assessed correlations between HDAC expression levels and clinical data and survival analysis. Results: Of the 91 cases examined, 46 (50.5%) were men and 45 (49.5%) were women. Most of the patients were elderly, and 74 (81.3%) cases were older than 46 y. Forty-six (50.5%) cases showed lymph node involvement, and 45 (49.5%) cases showed lymphoma at extranodal sites. In nodal lymphoma, staining was strongly positive for HDAC2, whereas staining was weak or negative for HDAC4; however, there was no significant correlation with survival. But nodal lymphoma cases with high nuclear expression of HDAC2 and nodal lymphoma cases with high nuclear expression of HDAC2 and low nuclear expression of HDAC4 showed significantly shorter survival times compared with other cases. Conclusions: High nuclear expression of HDAC2 may play an important role in survival of DLBCL patients, especially in those with nodal lymphoma, which is associated with a shorter survival time. Our results may have important implications for treatment of DLBCL by epigenetic regulation.
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影响因子：
3.8
作者：
Müller BM;Jana L;Kasajima A;Lehmann A;Prinzler J;Budczies J;Winzer KJ;Dietel M;Weichert W;Denkert C
通讯作者：
Denkert C
影响因子：
3.6
作者：
Tula-Sanchez AA;Havas AP;Alonge PJ;Klein ME;Doctor SR;Pinkston W;Glinsmann-Gibson BJ;Rimsza LM;Smith CL
通讯作者：
Smith CL
DOI：
10.1038/nrg2485
发表时间：
2009-01
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.4
作者：
Zain, Jasmine;O'Connor, Owen A.
通讯作者：
O'Connor, Owen A.
影响因子：
6.4
作者：
Cycon, Kelly A.;Mulvaney, Kathleen;Murphy, Shawn P.
通讯作者：
Murphy, Shawn P.