Mechanism of leukemogenesis by the inv(16) chimeric gene CBFB/PEBP2B-MHY11

被引:59
作者
Shigesada, K [1 ]
van de Sluis, B
Liu, PP
机构
[1] Kyoto Univ, Inst Virus Res, Dept Cell Biol, Kyoto 6068507, Japan
[2] NHGRI, Oncogenesis & Dev Sect, NIH, Bethesda, MD 20892 USA
关键词
CBF beta-MYH11; CBF beta-SMMHC; inv(16); leukemia; hematopoiesis;
D O I
10.1038/sj.onc.1207748
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Inv(16)(p13q22) is associated with acute myeloid leukemia subtype M4Eo that is characterized by the presence of myelomonocytic blasts and atypical eosinophils. This chromosomal rearrangement results in the fusion of CBFB and MYH11 genes. CBFbeta normally interacts with RUNX1 to form a transcriptionally active nuclear complex. The MYH11 gene encodes the smooth muscle myosin heavy chain. The CBFbeta-SMMHC fusion protein is capable of binding to RUNX1 and form dimers and multimers through its myosin tail. Previous results from transgenic mouse models show that Cbfb-MYH11 is able to inhibit dominantly Runx1 function in hematopoiesis, and is a key player in the pathogenesis of leukemia. In recent years, molecular and cellular biological studies have led to the proposal of several models to explain the function of CBFbeta-SMMHC. In this review, we will first focus our attention on the molecular mechanisms proposed in the recent publications. We will next examine recent gene expression pro. ling studies on inv(16) leukemia cells. Finally, we will describe a recent study from one of our labs on the identification of cooperating genes for leukemogenesis with CBFB-MYH11.
引用
收藏
页码:4297 / 4307
页数:11
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