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Acceleration of chronic myeloproliferation by enforced expression of Meis1 or Meis3 in Icsbp-deficient bone marrow cells

Oncogene volume 27, pages 3865–3869 (2008)Cite this article

Abstract

Identifying genetic pathways that cooperate in leukemogenesis facilitates our understanding of the molecular mechanisms at play. Interferon consensus sequence-binding protein (ICSBP) is a tumor suppressor, whose downregulation cooperates with BCR-ABL and NUP98-TOP1 gene products to accelerate leukemia induction in mouse models. Similarly, Meis1 synergizes with HoxA9 or NUP98-HOX (but not NUP98-TOP1) fusion genes to promote the early onset of leukemia. To investigate whether Icsbp deficiency interacts with Meis1 or its family member Meis3, we transplanted Icsbp−/− bone marrow (BM) cells after transduction with Meis1 or Meis3 retroviral vectors. Here, we show that enforced expression of Meis1 or Meis3 in Icsbp−/− BM cells induces a fatal, invasive myeloproliferative disease. Secondary mutations, such as activation of Mn1, led to the progression to acute myeloid leukemia in a few mice. Interestingly, expression of endogenous Meis1 and Meis3 mRNAs was repressed in the granulocytic progenitor population of Icsbp−/− mice. These results reveal a novel collaboration between Icsbp deficiency and Meis1/Meis3 in the acceleration of chronic myeloid leukemia-like disease.

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Acknowledgements

We thank Drs T Nakamura (Japanese Foundation for Cancer Research) and T Kitamura (Institute of Medical Science, University of Tokyo) for Meis1a cDNA and pMYs-IG vectors, respectively. We also thank Susanne Roscher and Silvia Dolski for assistance. This study was supported by the Human Science Foundation, the Ministry of Education, Culture, Sports, Science and Technology of Japan and the German José Carrreras Leukemia Foundation. The Heinrich-Pette-Institut is supported by the Freie und Hansestadt Hamburg and the Federal Ministry of Health and Social Security.

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Authors and Affiliations

  1. Stem Cell Project Group, The Tokyo Metropolitan Institute of Medical Science, Tokyo Metropolitan Organization for Medical Research, Tokyo, Japan

    T Hara, R Kazama, S Okamoto & K Minehata

  2. Molecular Pathology Group, Heinrich-Pette-Institut fur Experimentelle Immunologie and Virologie, Hamburg, Germany

    M Schwieger, M Ziegler, J Löhler & C Stocking

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  1. T Hara
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  2. M Schwieger
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  3. R Kazama
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  4. S Okamoto
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  8. C Stocking
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Correspondence to T Hara.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Hara, T., Schwieger, M., Kazama, R. et al. Acceleration of chronic myeloproliferation by enforced expression of Meis1 or Meis3 in Icsbp-deficient bone marrow cells. Oncogene 27, 3865–3869 (2008). https://doi.org/10.1038/sj.onc.1211043

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