MLL-AF9-Induced Leukemogenesis Requires Coexpression of the Wild-Type Mll Allele

被引:196
作者
Thiel, Austin T. [1 ]
Blessington, Peter [1 ]
Zou, Tao [2 ]
Feather, Danielle [1 ]
Wu, Xinjiang [1 ]
Yan, Jizhou [1 ]
Zhang, Hui [1 ]
Liu, Zuguo [3 ,4 ]
Ernst, Patricia [5 ,6 ]
Koretzky, Gary A. [2 ]
Hua, Xianxin [1 ]
机构
[1] Univ Penn, Dept Canc Biol, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA
[2] Univ Penn, Abramson Family Canc Res Inst, Dept Chem,Dept Bioengn, Dept Med,Dept Pathol & Lab Med, Philadelphia, PA 19104 USA
[3] Xiamen Univ, Inst Eye, Xiamen 361005, Fujian, Peoples R China
[4] Xiamen Univ, Affiliated Xiamen Eye Ctr, Xiamen 361005, Fujian, Peoples R China
[5] Dartmouth Med Sch, Dept Genet, Hanover, NH 03755 USA
[6] Dartmouth Med Sch, Norris Cotton Canc Ctr, Hanover, NH 03755 USA
基金
美国国家卫生研究院;
关键词
PARTIAL TANDEM DUPLICATION; MIXED-LINEAGE LEUKEMIA; TUMOR-SUPPRESSOR MENIN; ACUTE MYELOID-LEUKEMIA; HISTONE METHYLTRANSFERASE; TRANSCRIPTIONAL ELONGATION; H3K79; METHYLATION; GENE-EXPRESSION; PHD FINGER; STEM-CELLS;
D O I
10.1016/j.ccr.2009.12.034
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Oncogenic fusion proteins are capable of initiating tumorigenesis, but the role of their wild-type counterparts in this process is poorly understood. The mixed lineage leukemia (MLL) gene undergoes chromosomal translocations, resulting in the formation of oncogenic MILL fusion proteins (MLL-FPs). Here, we show that menin recruits both wild-type MLL and oncogenic MLL-AF9 fusion protein to the loci of HOX genes to activate their transcription. Wild-type MLL not only catalyzes histone methylation at key target genes but also controls distinct MLL-AF9-induced histone methylation. Notably, the wild-type MY allele is required for MLL-AF9-induced leukemogenesis and maintenance of MLL-AF9-transformed cells. These findings suggest an essential cooperation between an oncogene and its wild-type counterpart in MLL-AF9-induced leukemogenesis.
引用
收藏
页码:148 / 159
页数:12
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