组蛋白去甲基化酶 LSD1 抑制剂对 MLL-ENL白血病细胞诱导分化的研究

发育医学电子杂志

2015, Vol. 3

Issue (2): 91-95

临床遗传论著

组蛋白去甲基化酶 LSD1 抑制剂对 MLL-ENL白血病细胞诱导分化的研究

杨雪静^1,2　和夫红¹ 　黄伊子³　闫进¹　王前飞¹

杨雪静^1,2　和夫红¹ 　黄伊子³　闫进¹　王前飞¹（1.中国科学院北京基因组研究所，北京　100101；2.中国科学院大学，北京　100049；3.湖南农业大学，长沙　410128）

LSD1 inhibition induces differentiation of MLL-ENL leukemia cells

YANG Xue-jing1,2, HE Fu-hong¹, HUANG Yi-zi3, YAN Jin1, WANG Qian-fei1

1.Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; 2.University of the Chinese Academy of Sciences, Beijing 100049, China; 3. Hunan Agricultural University, Changsha 410128, China

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摘要目的　研究组蛋白去甲基化酶 LSD1 抑制剂对 MLL-ENL 亚型白血病细胞的影响，为 LSD1成为 MLL-ENL 亚型白血病的治疗新靶点提供证据。方法　首先采用 LSD1 酶活性抑制剂反式环苯丙胺 (TCP ) 处理细胞，通过细胞增殖、克隆形成实验和瑞士吉姆萨染色等实验技术，检测 LSD1 抑制剂处理对 MLL-ENL 白血病细胞的影响；进一步采用蛋白质印迹和 RT-PCR 实验技术，探索 LSD1 抑制在 MLL-ENL 白血病细胞中的作用机制。结果　LSD1 抑制剂处理显著降低 MLL-ENL 白血病细胞的增殖和克隆形成能力，并诱导细胞分化；LSD1 抑制剂处理后，组蛋白修饰 H3K4me2 整体水平升高，致癌基因 Bmi1 表达显著降低并且分化相关基因的表达被激活。结论　LSD1 抑制剂处理促进 MLL-ENL 白血病细胞分化并抑制白血病细胞生长，可能与组蛋白修饰 H3K4me2 改变后抑制关键致癌基因和激活分化基因有关。

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关键词: MLL-ENL 白血病 ')" href="#">MLL-ENL 白血病组蛋白去甲基化酶 LSD1 反式环苯丙胺二甲基化酸 4')" href="#">组蛋白 H3 赖氨酸 4

Abstract: Objective To investigate the effect of histone demethylase LSD1 inhibition on MLL-ENL leukemia cells. Method　An inducible MLL-ENL mouse leukemia cell line Csh3 was used as a model. The cells was first treated with LSD1 inhibitor TCP (Tranylcypromine) . The effect of MLL-ENL cells upon LSD1 inhibition were examined by cell proliferation assay, colony forming cell (CFC) assay and wright-giemsa staining. Furthermore, The global level of histone H3 lysine 4 dimethylation (H3K4me2) and the expression of specific oncogenes and differentiation related genes in MLL-ENL cells were determined using western blotting and RT-PCR respectively. Results　LSD1 inhibition significantly reduced cell proliferation and colony growth, and induced cell differentiation in MLL-ENL leukemia cells. Conclusions LSD1 inhibition down-regulated oncogenes expression and up-regulated differentiation related genes to induce MLL-ENL leukemia cells differentiation. LSD1 inhibition may be a promising treatment for MLL-ENL leukemia.

Key words: MLL-ENL leukemia ')" href="#"> MLL-ENL leukemia histone demethylase LSD1 TCP H3K4me2

收稿日期: 2014-11-24 出版日期: 2015-04-30 发布日期: 2018-05-25 期的出版日期: 2015-04-30

通讯作者: 王前飞https://baike.baidu.com/item/%E7%8E%8B%E5%89%8D%E9%A3%9E/186171?fr=aladdin E-mail: wangqf@big.ac.cn

引用本文:

杨雪静　和夫红　黄伊子　闫进王前飞. 组蛋白去甲基化酶 LSD1 抑制剂对 MLL-ENL白血病细胞诱导分化的研究[J]. 发育医学电子杂志, 2015, 3(2): 91-95.
YANG Xue-jing, HE Fu-hong, HUANG Yi-zi, YAN Jin, WANG Qian-fei. LSD1 inhibition induces differentiation of MLL-ENL leukemia cells. Journal of Developmental Medicine(Electronic Version), 2015, 3(2): 91-95.

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