Expression of histone deacetylases in lymphoma: implication for the development of selective inhibitors.
Expression of histone deacetylases in lymphoma: implication for the development of selective inhibitors.
复制标题
DOI：
10.1111/j.1365-2141.2009.07887.x
复制
发表时间：
2009-11
影响因子：
6.5
通讯作者：
Younes A
中科院分区：
文献类型：
--
作者：
Gloghini A;Buglio D;Khaskhely NM;Georgakis G;Orlowski RZ;Neelapu SS;Carbone A;Younes A
非选择性组蛋白去乙酰化酶（HDAC）抑制剂是一种治疗淋巴细胞恶性肿瘤的新方法。然而，由于HDAC酶在不同类型的癌症（包括淋巴细胞恶性肿瘤）中的模式尚不清楚，这些治疗方法仍然是经验主义的。我们在原发性淋巴样肿瘤细胞系和组织切片中检测了I类和II类hdac的表达。I类酶在研究的所有细胞系和原发肿瘤中均高表达，包括霍奇金淋巴瘤（HL）微环境中的非恶性反应细胞。HDAC表达变化最频繁的是HDAC6，在9/14（64%）的淋巴样细胞系和83/89（93%）的原发性淋巴瘤组织标本中，HDAC6弱表达或未检测到，包括50/52（96%）的弥漫性大b细胞淋巴瘤和18/22（82%）的经典HL。HDAC6低表达的细胞系表现出高乙酰化微管蛋白的异常表达，并且发现对I类HDAC抑制剂MGCD0103的生长抑制作用更为敏感。总的来说，我们的数据表明HDAC6在原发性淋巴瘤病例中很少表达，这表明它可能不是这些淋巴样恶性肿瘤的重要治疗靶点。
Unselective histone deacetylase (HDAC) inhibitors are a promising novel therapy for lymphoid malignancies. However, these treatments remain empiric as the pattern of HDAC enzymes in different types of cancer, including lymphoid malignancies, remains unknown. We examined the expression of class I and class II HDACs in a panel of cell lines and tissue sections from primary lymphoid tumors. Class I enzymes were highly expressed in all cell lines and primary tumors studied, including the non-malignant reactive cells in the Hodgkin lymphoma (HL) microenvironment. The most frequently altered HDAC expression was HDAC6, as it was either weakly expressed or undetected in 9/14 (64%) of lymphoid cell lines and in 83/89 (93%) of primary lymphoma tissue specimens, including 50/52 (96%) cases of diffuse large B-cell lymphoma, and 18/22 (82%) cases of classical HL. Cell lines that had low expression level of HDAC6 demonstrated aberrant expression of hyper-acetylated tubulin, and were found to be more sensitive to the growth inhibitory effects of the class I HDAC inhibitor MGCD0103. Collectively, our data demonstrate that HDAC6 is rarely expressed in primary lymphoma cases, suggesting that it may not be an important therapeutic target in these lymphoid malignancies.
登录
查看更多内容
影响因子：
64.8
作者：
Hubbert, C;Guardiola, A;Yao, TP
通讯作者：
Yao, TP
影响因子：
20.3
作者：
Buglio, Daniela;Georgakis, Georgios V.;Younes, Anas
通讯作者：
Younes, Anas
影响因子：
45.3
作者：
O'Connor, OA;Heaney, ML;Kelly, WK
通讯作者：
Kelly, WK
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：
--
作者：
Gogusev, J;Telvi, L;Nezelof, C
通讯作者：
Nezelof, C