CREBBP和EP300基因的体细胞突变影响恶性弥漫性大B细胞淋巴瘤（DLBCL）克隆对组蛋白去乙酰化酶抑制的反应。
Somatic mutations of the CREBBP and EP300 genes affect response to histone deacetylase inhibition in malignant DLBCL clones.
作者信息
Andersen Christen Lykkegaard, Asmar Fazila, Klausen Tobias, Hasselbalch Hans, Grønbæk Kirsten
机构信息
Department of Hematology, Roskilde University Hospital, Denmark ; Department of Hematology, Copenhagen University Hospital, Denmark.
Department of Hematology, Copenhagen University Hospital, Denmark.
出版信息
Leuk Res Rep. 2012 Dec 8;2(1):1-3. doi: 10.1016/j.lrr.2012.10.002. eCollection 2012.
Abstract
Heterogeneous clinical responses to histone deacetylase inhibitors (HDACi) in diffuse large B-cell lymphoma (DLBCL) have prompted a need for evaluating the impact of mutations in the histone acetyl transferases (HAT) CREBBP and EP300 on HDACi treatment outcome. We identified four DLBCL cell lines; Toledo, with mutations in CREBBP and EP300, SUDHL-7 with mutation of CREBBP and wild-type (wt) EP300, RL with mutation of EP300 and wt CREBBP, and U2932 with wt CREBBP and wt EP300. Vorinostat treatment induced apoptosis significantly more rapid and profound in the CREBBP/EP300 double mutant cell line. Our results suggest that pre-treatment stratification according to HAT defects may be relevant in DLBCL.
摘要
弥漫性大B细胞淋巴瘤（DLBCL）对组蛋白去乙酰化酶抑制剂（HDACi）的临床反应存在异质性，这促使人们需要评估组蛋白乙酰转移酶（HAT）CREBBP和EP300中的突变对HDACi治疗结果的影响。我们鉴定出了四株DLBCL细胞系；托莱多细胞系，其CREBBP和EP300存在突变；SUDHL - 7细胞系，其CREBBP发生突变而EP300为野生型（wt）；RL细胞系，其EP300发生突变而CREBBP为wt；以及U2932细胞系，其CREBBP和EP300均为wt。伏立诺他治疗在CREBBP/EP300双突变细胞系中诱导凋亡的速度明显更快且程度更深。我们的结果表明，根据HAT缺陷进行预处理分层在DLBCL中可能具有相关性。
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本文引用的文献
1
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Leuk Res. 2012 Apr;36(4):485-7. doi: 10.1016/j.leukres.2011.11.018. Epub 2011 Dec 15.
2
Histone modifiers in cancer: friends or foes?癌症中的组蛋白修饰因子：是友还是敌？
Genes Cancer. 2011 Jun;2(6):631-47. doi: 10.1177/1947601911417176.
3
The impact of acetylation and deacetylation on the p53 pathway.乙酰化和去乙酰化对 p53 通路的影响。
Protein Cell. 2011 Jun;2(6):456-62. doi: 10.1007/s13238-011-1063-9. Epub 2011 Jul 12.
4
CREBBP mutations in relapsed acute lymphoblastic leukaemia.复发急性淋巴细胞白血病中的 CREBBP 突变。
Nature. 2011 Mar 10;471(7337):235-9. doi: 10.1038/nature09727.
5
Inactivating mutations of acetyltransferase genes in B-cell lymphoma.B 细胞淋巴瘤中乙酰转移酶基因的失活突变。
Nature. 2011 Mar 10;471(7337):189-95. doi: 10.1038/nature09730.
6
Expanded binding specificity of the human histone chaperone NASP.人类组蛋白伴侣NASP扩展的结合特异性
Nucleic Acids Res. 2008 Oct;36(18):5763-72. doi: 10.1093/nar/gkn574. Epub 2008 Sep 9.
7
The BCL6 proto-oncogene suppresses p53 expression in germinal-centre B cells.BCL6原癌基因抑制生发中心B细胞中的p53表达。
Nature. 2004 Dec 2;432(7017):635-9. doi: 10.1038/nature03147.
8
Acetylation inactivates the transcriptional repressor BCL6.乙酰化使转录抑制因子BCL6失活。
Nat Genet. 2002 Dec;32(4):606-13. doi: 10.1038/ng1018. Epub 2002 Oct 28.
9
Overlapping but distinct patterns of histone acetylation by the human coactivators p300 and PCAF within nucleosomal substrates.人类共激活因子p300和PCAF在核小体底物上的组蛋白乙酰化模式相互重叠但又有所不同。
J Biol Chem. 1999 Jan 15;274(3):1189-92. doi: 10.1074/jbc.274.3.1189.
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