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Suppression of Pu.1 function results in expanded myelopoiesis in zebrafish

Leukemia volume 27, pages 1913–1917 (2013)Cite this article

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PU.1 is a member of Ets-family transcription factors, which is indispensable for generating early myeloid progenitors1 and for the determination of monocytic versus granulocytic lineages during myelopoiesis.2, 3 Apart from its early function in myelopoiesis, PU.1 is also reported to be involved in leukemogenesis in mice and human.4 It has been shown that PU.1 expression is downregulated in human acute myeloid leukemia (AML) patients,5, 6 and PU.1 mutations are found in about 7% of the patients in a study involving 126 AML patients.7 Likewise, reduction of PU.1 activity leads to AML in mice.8, 9

Owing to its unique advantages, zebrafish has been utilized as a promising model for studying many aspects of developmental biology and human diseases.10 Through targeting induced local lesions in genomes (TILLING) approach, we obtained a hypomorphic pu.1 zebrafish allele (pu.1G242D), which harbors a point mutation in the DNA binding domain of the Pu.1 protein.3 This mutation does not affect pu.1 transcription but destabilize Pu.1 protein, resulting in a reduction of Pu.1 activity.3

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant No.: 81270631; Grant No.: 31271564); the National Basic Research Program of China (Grant No.: 2012CB945102); Guangdong Province International Science and Technology Cooperation Program (Grant No.: 2010B05100017), Guangzhou Science and Technology Support Program (Grant No.: 11A62121172), and the General Research Fund from the Research Grants Council of HKSAR (Grant No.: HKUST6/CRF/09).

Author-contributions

JPS, WL, LL, JHC and MW designed the research, performed experiments and analyzed data. YYZ, AYL, WQZ, ZLW and WJL designed the research and analyzed data.

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Author notes

  1. J Sun and W Liu: These authors contribute equally to this work.

Authors and Affiliations

  1. Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China

    J Sun & W Liao

  2. Department of Cell Biology, Key Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases of Guangdong Higher Education Institutes, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China

    W Liu, J Chen, M Wu, Y Zhang & W Zhang

  3. The Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, State Key Laboratory Breeding Base of Eco-Environments and Bio-Resources of the Three Gorges Area, School of Life Science, Southwest University, Chongqing, China

    L Li

  4. Department of Medicine, LKS Faculty of Medicine, Queen Mary Hospital, Hong Kong, China

    A Y H Leung

  5. Division of Life Science, State Key Laboratory of Molecular Neuroscience, the Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China

    Z Wen

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  1. J Sun
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  2. W Liu
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Corresponding authors

Correspondence to W Zhang, Z Wen or W Liao.

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Sun, J., Liu, W., Li, L. et al. Suppression of Pu.1 function results in expanded myelopoiesis in zebrafish. Leukemia 27, 1913–1917 (2013). https://doi.org/10.1038/leu.2013.67

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