Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukaemia.
Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukaemia.
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DOI：
10.1038/ncomms13331
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发表时间：
2016-11-08
影响因子：
16.6
通讯作者：
Mullighan, Charles G.
中科院分区：
文献类型：
--
作者：
Gu, Zhaohui;Churchman, Michelle;Roberts, Kathryn;Li, Yongjin;Liu, Yu;Harvey, Richard C.;McCastlain, Kelly;Reshmi, Shalini C.;Payne-Turner, Debbie;Iacobucci, Ilaria;Shao, Ying;Chen, I-Ming;Valentine, Marcus;Pei, Deqing;Mungall, Karen L.;Mungall, Andrew J.;Ma, Yussanne;Moore, Richard;Marra, Marco;Stonerock, Eileen;Gastier-Foster, Julie M.;Devidas, Meenakshi;Dai, Yunfeng;Wood, Brent;Borowitz, Michael;Larsen, Eric E.;Maloney, Kelly;Mattano, Leonard A., Jr.;Angiolillo, Anne;Salzer, Wanda L.;Burke, Michael J.;Gianni, Francesca;Spinelli, Orietta;Radich, Jerald P.;Minden, Mark D.;Moorman, Anthony V.;Patel, Bella;Fielding, Adele K.;Rowe, Jacob M.;Luger, Selina M.;Bhatia, Ravi;Aldoss, Ibrahim;Forman, Stephen J.;Kohlschmidt, Jessica;Mrozek, Krzysztof;Marcucci, Guido;Bloomfield, Clara D.;Stock, Wendy;Kornblau, Steven;Kantarjian, Hagop M.;Konopleva, Marina;Paietta, Elisabeth;Willman, Cheryl L.;Loh, Mignon L.;Hunger, Stephen P.;Mullighan, Charles G.
染色体重排是急性淋巴细胞白血病（ALL）的起始事件。在此，我们通过对560例ALL病例进行RNA测序，在22例具有独特基因表达谱的B祖细胞ALL（B - ALL）病例中鉴定出MEF2D（肌细胞增强因子2D）与5个基因（BCL9、CSF1R、DAZAP1、HNRNPUL1和SS18）之间的重排，其中最常见的是MEF2D - BCL9。对1164例B - ALL病例的扩大队列进行检查，发现30例存在MEF2D重排，其中包括一个额外的融合伴侣FOXJ2；因此，在缺乏反复改变的病例中，MEF2D重排病例占5.3%。MEF2D重排的ALL具有独特的免疫表型、重排位点的DNA拷贝数改变、诊断年龄较大以及预后不良的特点。这些重排导致MEF2D转录活性增强、淋巴细胞转化、HDAC9表达激活以及对组蛋白去乙酰化酶抑制剂治疗敏感。因此，MEF2D重排的ALL代表一种独特的高危白血病形式，应考虑新的治疗方法。
急性淋巴细胞白血病以染色体重排为特征。在此，作者对一大群患者进行RNA测序，并鉴定出MEF2D的反复重排，这导致该基因转录活性增加以及体外细胞转化。
Chromosomal rearrangements are initiating events in acute lymphoblastic leukaemia (ALL). Here using RNA sequencing of 560 ALL cases, we identify rearrangements between MEF2D (myocyte enhancer factor 2D) and five genes (BCL9, CSF1R, DAZAP1, HNRNPUL1 and SS18) in 22 B progenitor ALL (B-ALL) cases with a distinct gene expression profile, the most common of which is MEF2D-BCL9. Examination of an extended cohort of 1,164 B-ALL cases identified 30 cases with MEF2D rearrangements, which include an additional fusion partner, FOXJ2; thus, MEF2D-rearranged cases comprise 5.3% of cases lacking recurring alterations. MEF2D-rearranged ALL is characterized by a distinct immunophenotype, DNA copy number alterations at the rearrangement sites, older diagnosis age and poor outcome. The rearrangements result in enhanced MEF2D transcriptional activity, lymphoid transformation, activation of HDAC9 expression and sensitive to histone deacetylase inhibitor treatment. Thus, MEF2D-rearranged ALL represents a distinct form of high-risk leukaemia, for which new therapeutic approaches should be considered. Acute lymphoblastic leukaemia is characterized by chromosomal rearrangements. Here, the authors carry out RNA-sequencing on a large cohort of patients and identify recurrent rearrangements of MEF2D, which lead to increased transcriptional activity of the gene, and cellular transformation in vitro.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
20.3
作者：
Harvey, Richard C.;Mullighan, Charles G.;Willman, Cheryl L.
通讯作者：
Willman, Cheryl L.
影响因子：
15
作者：
Hoggard, Logan R.;Zhang, Yongqiang;Ji, Haitao
通讯作者：
Ji, Haitao
影响因子：
20.3
作者：
Herglotz, Julia;Unrau, Ludmilla;Stocking, Carol
通讯作者：
Stocking, Carol
影响因子：
5.3
作者：
Haberland, Michael;Arnold, Michael A.;Olson, Eric N.
通讯作者：
Olson, Eric N.