IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v8y2017i1d10.1038_ncomms14616.html
   My bibliography  Save this article

Genetic and regulatory mechanism of susceptibility to high-hyperdiploid acute lymphoblastic leukaemia at 10q21.2

Author

Listed:
  • James B. Studd

    (The Institute of Cancer Research)

  • Jayaram Vijayakrishnan

    (The Institute of Cancer Research)

  • Minjun Yang

    (Lund University)

  • Gabriele Migliorini

    (The Institute of Cancer Research)

  • Kajsa Paulsson

    (Lund University)

  • Richard S. Houlston

    (The Institute of Cancer Research
    The Institute of Cancer Research)

Abstract

Despite high-hyperdiploid acute lymphoblastic leukaemia (HD-ALL) being the most common subgroup of paediatric ALL, its aetiology remains unknown. Genome-wide association studies have demonstrated association at 10q21.2. Here, we sought to determine how this region influences HD-ALL risk. We impute genotypes across the locus, finding the single nucleotide polymorphism rs7090445 highly associated with HD-ALL (P=1.54 × 10−38), and residing in a predicted enhancer element. We show this region physically interacts with the transcription start site of ARID5B, that alleles of rs7090445 have differential enhancer activity and influence RUNX3 binding. RUNX3 knock-down reduces ARID5B expression and rs7090445 enhancer activity. Individuals carrying the rs7090445-C risk allele also have reduced ARID5B expression. Finally, the rs7090445-C risk allele is preferentially retained in HD-ALL blasts consistent with inherited genetic variation contributing to arrest of normal lymphocyte development, facilitating leukaemic clonal expansion. These data provide evidence for a biological mechanism underlying hereditary risk of HD-ALL at 10q21.2.

Suggested Citation

  • James B. Studd & Jayaram Vijayakrishnan & Minjun Yang & Gabriele Migliorini & Kajsa Paulsson & Richard S. Houlston, 2017. "Genetic and regulatory mechanism of susceptibility to high-hyperdiploid acute lymphoblastic leukaemia at 10q21.2," Nature Communications, Nature, vol. 8(1), pages 1-9, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14616
    DOI: 10.1038/ncomms14616
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms14616
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms14616?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Kashi Raj Bhattarai & Robert J. Mobley & Kelly R. Barnett & Daniel C. Ferguson & Baranda S. Hansen & Jonathan D. Diedrich & Brennan P. Bergeron & Satoshi Yoshimura & Wenjian Yang & Kristine R. Crews &, 2024. "Investigation of inherited noncoding genetic variation impacting the pharmacogenomics of childhood acute lymphoblastic leukemia treatment," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Han Wang & Huiying Sun & Bilin Liang & Fang Zhang & Fan Yang & Bowen Cui & Lixia Ding & Xiang Wang & Ronghua Wang & Jiaoyang Cai & Yanjing Tang & Jianan Rao & Wenting Hu & Shuang Zhao & Wenyan Wu & Xi, 2023. "Chromatin accessibility landscape of relapsed pediatric B-lineage acute lymphoblastic leukemia," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14616. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.