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Mouse models for core binding factor leukemia

Leukemia volume 29, pages 1970–1980 (2015)Cite this article

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Abstract

RUNX1 and CBFB are among the most frequently mutated genes in human leukemias. Genetic alterations such as chromosomal translocations, copy number variations and point mutations have been widely reported to result in the malfunction of RUNX transcription factors. Leukemias arising from such alterations in RUNX family genes are collectively termed core binding factor (CBF) leukemias. Although adult CBF leukemias generally are considered a favorable risk group as compared with other forms of acute myeloid leukemia, the 5-year survival rate remains low. An improved understanding of the molecular mechanism for CBF leukemia is imperative to uncover novel treatment options. Over the years, retroviral transduction-transplantation assays and transgenic, knockin and knockout mouse models alone or in combination with mutagenesis have been used to study the roles of RUNX alterations in leukemogenesis. Although successful in inducing leukemia, the existing assays and models possess many inherent limitations. A CBF leukemia model which induces leukemia with complete penetrance and short latency would be ideal as a platform for drug discovery. Here, we summarize the currently available mouse models which have been utilized to study CBF leukemias, discuss the advantages and limitations of individual experimental systems, and propose suggestions for improvements of mouse models.

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Acknowledgements

This work was supported by National Medical Research Council, Singapore National Research Foundation, Ministry of Education under the Research Center of Excellence programme, A*STAR (Agency of Science Technology and Research) and Biomedical Research Council.

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Authors and Affiliations

  1. Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

    D W L Chin, N Watanabe-Okochi, C Q Wang & M Osato

  2. Institute of Molecular and Cell Biology, A*STAR, Singapore, Singapore

    C Q Wang & V Tergaonkar

  3. Institute of Bioengineering and Nanotechnology, A*STAR, Singapore, Singapore

    M Osato

  4. Department of Paediatrics, National University of Singapore, Singapore, Singapore

    M Osato

  5. International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Japan

    M Osato

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  3. C Q Wang
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  4. V Tergaonkar
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  5. M Osato
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Correspondence to M Osato.

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Chin, D., Watanabe-Okochi, N., Wang, C. et al. Mouse models for core binding factor leukemia. Leukemia 29, 1970–1980 (2015). https://doi.org/10.1038/leu.2015.181

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