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急性髓系白血病细胞中FOP2-FGFR1基因融合破坏后维生素D受体表达恢复及对1,25-二羟维生素D3敏感性增强。

Restored expression of vitamin D receptor and sensitivity to 1,25-dihydroxyvitamin D3 in response to disrupted fusion FOP2-FGFR1 gene in acute myeloid leukemia cells.

作者信息

Marchwicka Aleksandra, Corcoran Aoife, Berkowska Klaudia, Marcinkowska Ewa

机构信息

Laboratory of Protein Biochemistry, Faculty of Biotechnology, University of Wroclaw, Joliot-Curie 14a, 50-383 Wroclaw, Poland.

出版信息

Cell Biosci. 2016 Feb 2;6:7. doi: 10.1186/s13578-016-0075-9. eCollection 2016.

DOI:10.1186/s13578-016-0075-9
PMID:26839680
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4735962/
Abstract

BACKGROUND

Acute myeloid leukemia (AML) cells can be induced to undergo terminal differentiation with subsequent loss of tumorigenicity using 1,25-dihydroxyvitamin D3 (1,25D) alone or in combination with hematopoietic cytokines. KG1 cells are resistant to 1,25D-induced cell differentiation. These cells have the aberrant signal transduction resulting from a constitutively active fusion protein FOP2-FGFR1, a constitutively active STAT1 and a high level of interferon (IFN) stimulated genes (ISGs).

METHODS

In this paper we report that in KG1 cells with constitutively activated protein FOP2-FGFR1 delivery of plasmid DNA disrupted FOP2-FGFR1 fusion gene.

RESULTS

As a consequence, STAT1 signal transduction pathway became switched off, the expression of vitamin D receptor (VDR) gene was increased and sensitivity to 1,25D-induced differentiation was restored. The activation of ISGs in KG1 cells resulted in resistance to externally added IFNs, and also this effect was reversed in cells with disrupted FOP2-FGFR1 fusion gene.

DISCUSSION

In this paper we have documented for the first time a link between constitutively active STAT1 signal transduction pathway, high level of ISGs and low expression of VDR gene.

CONCLUSIONS

We show in this paper that delivery of plasmid DNA to the cells may disrupt fusion gene FOP2-FGFR1 which occurs in a disease entity called 8p11 myeloproliferative syndrome. Inhibition of the FOP2-FGFR1 signal transduction pathway restored sensitivity of the cells to 1,25D-induced cell differentiation.

摘要

背景

急性髓系白血病（AML）细胞可通过单独使用1,25 - 二羟基维生素D3（1,25D）或与造血细胞因子联合使用，诱导其进行终末分化并随后丧失致瘤性。KG1细胞对1,25D诱导的细胞分化具有抗性。这些细胞具有由组成型活性融合蛋白FOP2 - FGFR1、组成型活性STAT1和高水平的干扰素（IFN）刺激基因（ISG）导致的异常信号转导。

方法

在本文中，我们报道在具有组成型活化蛋白FOP2 - FGFR1的KG1细胞中，质粒DNA的递送破坏了FOP2 - FGFR1融合基因。

结果

结果，STAT1信号转导通路被关闭，维生素D受体（VDR）基因的表达增加，并且对1,25D诱导的分化的敏感性得以恢复。KG1细胞中ISG的激活导致对外部添加的IFN具有抗性，并且在FOP2 - FGFR1融合基因被破坏的细胞中这种效应也被逆转。

讨论

在本文中，我们首次记录了组成型活性STAT1信号转导通路、高水平的ISG与VDR基因低表达之间的联系。

结论

我们在本文中表明，将质粒DNA递送至细胞可能破坏在一种称为8p11骨髓增殖综合征的疾病实体中出现的融合基因FOP2 - FGFR1。抑制FOP2 - FGFR1信号转导通路恢复了细胞对1,25D诱导的细胞分化的敏感性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1932/4735962/d39b52677a04/13578_2016_75_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1932/4735962/edb1ca922344/13578_2016_75_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1932/4735962/a96876f8bbe1/13578_2016_75_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1932/4735962/2ac4d02afc53/13578_2016_75_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1932/4735962/508bdd988f78/13578_2016_75_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1932/4735962/f261810b931c/13578_2016_75_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1932/4735962/9ad77bdc108a/13578_2016_75_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1932/4735962/d39b52677a04/13578_2016_75_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1932/4735962/edb1ca922344/13578_2016_75_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1932/4735962/45687d5fab77/13578_2016_75_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1932/4735962/a96876f8bbe1/13578_2016_75_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1932/4735962/2ac4d02afc53/13578_2016_75_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1932/4735962/508bdd988f78/13578_2016_75_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1932/4735962/f261810b931c/13578_2016_75_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1932/4735962/9ad77bdc108a/13578_2016_75_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1932/4735962/d39b52677a04/13578_2016_75_Fig8_HTML.jpg

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本文引用的文献

1
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J Cell Biochem. 2015 Aug;116(8):1500-12. doi: 10.1002/jcb.25104.
2
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Mol Aspects Med. 2015 Feb;41:1-115. doi: 10.1016/j.mam.2014.12.003. Epub 2014 Dec 25.
3
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J Clin Med. 2022 Apr 15;11(8):2224. doi: 10.3390/jcm11082224.
4
Investigating the Role of Methylation in Silencing of Gene Expression in Normal Cells during Hematopoiesis and in Their Leukemic Counterparts.研究甲基化在造血过程中正常细胞基因表达沉默及其白血病对应物中的作用。
Cells. 2020 Aug 29;9(9):1991. doi: 10.3390/cells9091991.
5
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6
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7
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8
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9
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10
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