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Identification of four novel associations for B-cell acute lymphoblastic leukaemia risk

Author

Listed:
  • Jayaram Vijayakrishnan

    (The Institute of Cancer Research)

  • Maoxiang Qian

    (St. Jude Children’s Research Hospital
    Fudan University)

  • James B. Studd

    (The Institute of Cancer Research)

  • Wenjian Yang

    (St. Jude Children’s Research Hospital)

  • Ben Kinnersley

    (The Institute of Cancer Research)

  • Philip J. Law

    (The Institute of Cancer Research)

  • Peter Broderick

    (The Institute of Cancer Research)

  • Elizabeth A. Raetz

    (New York University Langone Health)

  • James Allan

    (Newcastle University)

  • Ching-Hon Pui

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

  • Ajay Vora

    (Great Ormond Hospital)

  • William E. Evans

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

  • Anthony Moorman

    (Newcastle University)

  • Allen Yeoh

    (National University of Singapore
    Khoo Teck Puat–National University Children’s Medical Institute, National University Hospital, National University Health System)

  • Wentao Yang

    (St. Jude Children’s Research Hospital)

  • Chunliang Li

    (St. Jude Children’s Research Hospital)

  • Claus R. Bartram

    (University Hospital)

  • Charles G. Mullighan

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

  • Martin Zimmerman

    (Hannover Medical School)

  • Stephen P. Hunger

    (Children’s Hospital of Philadelphia and the Perelman School of Medicine at The University of Pennsylvania)

  • Martin Schrappe

    (University Medical Centre Schleswig-Holstein)

  • Mary V. Relling

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

  • Martin Stanulla

    (Hannover Medical School)

  • Mignon L. Loh

    (University of California San Francisco)

  • Richard S. Houlston

    (The Institute of Cancer Research)

  • Jun J. Yang

    (St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital
    St. Jude Children’s Research Hospital)

Abstract

There is increasing evidence for a strong inherited genetic basis of susceptibility to acute lymphoblastic leukaemia (ALL) in children. To identify new risk variants for B-cell ALL (B-ALL) we conducted a meta-analysis with four GWAS (genome-wide association studies), totalling 5321 cases and 16,666 controls of European descent. We herein describe novel risk loci for B-ALL at 9q21.31 (rs76925697, P = 2.11 × 10−8), for high-hyperdiploid ALL at 5q31.1 (rs886285, P = 1.56 × 10−8) and 6p21.31 (rs210143 in BAK1, P = 2.21 × 10−8), and ETV6-RUNX1 ALL at 17q21.32 (rs10853104 in IGF2BP1, P = 1.82 × 10−8). Particularly notable are the pleiotropic effects of the BAK1 variant on multiple haematological malignancies and specific effects of IGF2BP1 on ETV6-RUNX1 ALL evidenced by both germline and somatic genomic analyses. Integration of GWAS signals with transcriptomic/epigenomic profiling and 3D chromatin interaction data for these leukaemia risk loci suggests deregulation of B-cell development and the cell cycle as central mechanisms governing genetic susceptibility to ALL.

Suggested Citation

  • Jayaram Vijayakrishnan & Maoxiang Qian & James B. Studd & Wenjian Yang & Ben Kinnersley & Philip J. Law & Peter Broderick & Elizabeth A. Raetz & James Allan & Ching-Hon Pui & Ajay Vora & William E. Ev, 2019. "Identification of four novel associations for B-cell acute lymphoblastic leukaemia risk," Nature Communications, Nature, vol. 10(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13069-6
    DOI: 10.1038/s41467-019-13069-6
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