Mixed lineage leukemia plays a critical role in estrogen-mediated regulation of HOXA10 in acute myelocytic leukemia cells

Yao Jie; Fang Lichao; Zheng Junsong

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Mixed lineage leukemia plays a critical role in estrogen-mediated regulation of HOXA10 in acute myelocytic leukemia cells

更新时间：2025-01-15

- Mixed lineage leukemia plays a critical role in estrogen-mediated regulation of HOXA10 in acute myelocytic leukemia cells
- Journal of Army Medical University Vol. 35, Issue 17, Pages: 1797-1800(2013)
- 作者机构：
  
  第三军医大学医学检验系临床检验学教研室
- 作者简介：
- 基金信息：
- DOI：
  CLC： R363.21;R394.3;R733.71
- Published：2013，
  
  Published Online：15 September 2013，
- 稿件说明：
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YAO JIE, FANG LICHAO, ZHENG JUNSONG. Mixed lineage leukemia plays a critical role in estrogen-mediated regulation of HOXA10 in acute myelocytic leukemia cells. [J]. Journal of army medical university, 2013, 35(17): 1797-1800.
DOI：

YAO JIE, FANG LICHAO, ZHENG JUNSONG. Mixed lineage leukemia plays a critical role in estrogen-mediated regulation of HOXA10 in acute myelocytic leukemia cells. [J]. Journal of army medical university, 2013, 35(17): 1797-1800. DOI：

摘要

目的通过研究在急性髓性白血病细胞中HOXA10表达调控机制

探讨HOXA10调控作为AML防治新靶点的可能性。方法以不同剂量雌二醇（E

）在不同时间点刺激急性粒细胞白血病细胞株（HL-60），以不刺激的HL-60细胞作参照应用RT-PCR检测HOXA10基因表达活性的差异明确E

对HOXA10表达的活化作用

并在E

刺激下以反义寡核苷酸转染技术分别敲除ERα 、ERβ和 MLLs(MLL1-4)后再检测HOXA10 mRNA和蛋白表达的变化确定哪一种雌激素受体的活化与HOXA10的表达相关，哪一种MLL对HOXA10表达有调控作用。以ChIP 实验检测MLL 和HOXA10 的相互作用，再以Western blot 检测E

刺激前后组蛋白H3K4甲基化状态以明确MLL是否通过表观遗传学途径调控HOXA10的表达。结果在E

50 nmol/L 6 h刺激下HOXA10表达明显升高，ERα和ERβ反义寡核苷酸转染后HOXA10表达均有下降，MLL1表达沉默时HOXA10表达明显降低（

0.05），MLL1可以结合到HOXA10启动子上的ERE区域而组蛋白H3K4甲基化状态在E

刺激后明显高于刺激前（

0.05）。结论急性髓性白血病细胞的HOXA10基因表达受MLL1蛋白调控，可能为急性髓性白血病的致病机制分析提供了一个新的方向

MLL1介导的HOXA10表达的改变有可能成为急性髓性白血病的防治新靶点。

Abstract

Objective To investigate the expression of HOXA10 in acute myelocytic leukemia cells

and to find the regulating mechanism of HOXA10 expression in acute myelocytic leukemia cells. Methods RT-PCR and Western blotting were applied to detect HOXA10 mRNA and protein expression in

acute myelocytic leukemia HL-60 cells with knockdown of ERα

ERβ and mix lineage leukemia (MLLs) (MLL1-4)

respectively

and with or without treatment of estradiol (E

). ChIP was used to check the interaction between MLL and HOXA10

and Western blotting was used to check the methylation status of histone H3K4. Results E

could elevate HOXA10 expression through activation of ERα and ERβ. HOXA10 expression could be down-regulated by MLL1 knockdown. MLL1 could bind to the ERE region on HOXA10 promoter sequence. Conclusion This study may provide a new direction to study the pathogenic mechanism of acute myelocytic leukemia

and indicates that MLL1 can be a potential target for prevention and treatment of leukemia.

关键词

HOXA10混合系白血病基因雌激素受体急性髓性白血病

Keywords

HOXA10mix lineage leukemiaestrogen receptoracute myelocytic leukemia

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