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Oncogenes, Fusion Genes and Tumor Suppressor Genes

Enhanced expression of FHL2 leads to abnormal myelopoiesis in vivo

Leukemia volume 23, pages 1650–1657 (2009)Cite this article

Abstract

FHL2 is a multifunctional LIM domain protein that acts as a transcriptional modulator mediating proliferation and apoptosis in a tissue-specific manner. Upregulation of FHL2 has been detected in a variety of cancers. We demonstrate that upregulation of FHL2 is associated with a subset of acute myeloid leukemia with a characteristic gene-expression signature, and abnormalities of chromosome 5. In mice, expression of endogenous Fhl2 is downregulated coordinately during the differentiation of hematopoietic cells. Upregulation of FHL2 enhances proliferation of myeloid progenitor cells, and serial-replating efficiency of hematopoietic cells in vitro. Chimeric mice with enforced expression of FHL2 in bone marrow cells, are characterized by an expanded pool of myeloid progenitor cells, enhanced granulopoi esis and megakaryocytopoiesis. In addition, enhanced expression of FHL2 promotes cell-cycle entry of myeloid progenitor cells and increases the frequency of apoptosis of bone marrow cells in vivo. These results raise the possibility that deregulation of FHL2 contributes to the development of human myeloid disorders.

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Acknowledgements

This work was supported by PHS grant CA40046 (MML), the American Cancer Society (IRG-58-004-44; ZQ), and the American Cancer Society Illinois Division (05-22; ZQ) We are grateful to members of the Le Beau Laboratory, and to Dr Lucy A Godley, Dr John D Crispino and Dr Kevin M Shannon for helpful discussions.

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Authors and Affiliations

  1. Section of Hematology/Oncology and the Cancer Research Center, University of Chicago, Chicago, IL, USA

    Z Qian, L Mao, A A Fernald, H Yu, R Luo, Y Jiang & M M Le Beau

  2. Department of Pathology, University of Chicago, Chicago, IL, USA

    J Anastasi

  3. Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands

    P J Valk & R Delwel

Authors
  1. Z Qian
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  2. L Mao
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  3. A A Fernald
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  4. H Yu
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  6. Y Jiang
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  7. J Anastasi
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  8. P J Valk
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  9. R Delwel
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  10. M M Le Beau
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Correspondence to Z Qian.

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

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Qian, Z., Mao, L., Fernald, A. et al. Enhanced expression of FHL2 leads to abnormal myelopoiesis in vivo. Leukemia 23, 1650–1657 (2009). https://doi.org/10.1038/leu.2009.78

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