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

Oncogene volume 23, pages 4297–4307 (2004)Cite this article

Abstract

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. CBFβ normally interacts with RUNX1 to form a transcriptionally active nuclear complex. The MYH11 gene encodes the smooth muscle myosin heavy chain. The CBFβ-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 CBFβ-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 profiling 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.

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Acknowledgements

KS expresses special gratitude to Huang Gang and Hee-Jun Wee for their overwhelming contributions to detailed functional characterization of CBFβ/PEBP2β-SMMHC as well as their valuable discussions on which the section ‘Molecular basis for the dominant inhibition of RUNX1-dependent transcription by CBFβ-SMMHC’ is essentially based. PPL thanks Lucio Castilla for the retroviral insertion data and John Bushweller for critical reading of the manuscript.

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  1. Department of Cell Biology, Institute for Virus Research, Kyoto University, Kyoto, 606-8507, Japan

    Katsuya Shigesada

  2. Oncogenesis and Development Section, National Human Genome Research Institute, NIH, Bethesda, 20892, MD, USA

    Bart van de Sluis & P Paul Liu

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  1. Katsuya Shigesada
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  2. Bart van de Sluis
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Correspondence to Katsuya Shigesada or P Paul Liu.

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Shigesada, K., van de Sluis, B. & Liu, P. Mechanism of leukemogenesis by the inv(16) chimeric gene CBFB/PEBP2B-MHY11. Oncogene 23, 4297–4307 (2004). https://doi.org/10.1038/sj.onc.1207748

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