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Identification of an acute myeloid leukaemia associated noncoding somatic mutation at 3\(^\prime \) end of HOXA cluster

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Abstract

Noncoding somatic mutations have been demonstrated to play important role in tumourigenesis. Here we show that there exists an acute myeloid leukaemia associated noncoding somatic mutation at 3\(^\prime \) terminal of conserved HOXA cluster. The mutation was identified in the bone marrow blasts but not peripheral blood mononuclear cells or buccal cells of two M3 (acute promyelocytic leukaemia, APL) type patients from 45 acute myeloid leukaemia patients. The mutation also existed in a pair of twins one of them developed acute myeloid leukaemia M4 (acute myelomonocytic leukaemia) type. The mutation resides in about 2-kb downstream of HOXA1 gene where a functional retinoic acid response element is located and also bound by histone demethylase KDM3B. Reporter assay showed that the mutation results in the upregulation of transcriptional activity and unresponsiveness to retinoic acid receptor. To sum up, we identified a new acute myeloid leukaemia associated noncoding somatic mutation.

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Acknowledgements

This research was funded by the National Natural Science Foundation of China (NSFC) grant #81370628 and #81570157. Xin Xu was funded by the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry, Shandong Provincial Natural Science Foundation, China (#ZR2015CL023), Shandong Province Higher Educational Science and Technology Program (J16LL54), Weifang City Science and Technology Project 2018GX079. Lin Wang was funded by Weifang City Science and Technology Project (2015GX019). Chunling Zhao was funded by NSFC grant #81572578 and Shandong Provincial Natural Science Foundation, China #ZR2015HM028.

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Authors and Affiliations

  1. Laboratory for Stem Cell and Regenerative Medicine, the Affiliated Hospital of Weifang Medical University, Weifang,  261053, Shandong, People’s Republic of China

    Xin Xu, Lei Song, Yao Zhao, Xinjing Zhang, Zhenming Shen & Zhenbo Hu

  2. College of Bioscience and Technology, Weifang Medical University, Weifang, Shandong,  261053, People’s Republic of China

    Xin Xu & Chunling Zhao

  3. The School of Physics and Optoelectronic Engineering, Weifang University, Weifang, Shandong,  261061, People’s Republic of China

    Lin Wang

Authors
  1. Xin Xu
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  2. Lei Song
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  3. Yao Zhao
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  4. Lin Wang
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  5. Xinjing Zhang
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  6. Zhenming Shen
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  7. Chunling Zhao
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  8. Zhenbo Hu
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Correspondence to Xin Xu or Zhenbo Hu.

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Corresponding Editor: Indrajit Nanda

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Xu, X., Song, L., Zhao, Y. et al. Identification of an acute myeloid leukaemia associated noncoding somatic mutation at 3\(^\prime \) end of HOXA cluster. J Genet 98, 35 (2019). https://doi.org/10.1007/s12041-019-1081-6

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  • DOI: https://doi.org/10.1007/s12041-019-1081-6

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