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Disruption of the tumour-associated EMP3 enhances erythroid proliferation and causes the MAM-negative phenotype

Author

Listed:
  • Nicole Thornton

    (International Blood Group Reference Laboratory, NHS Blood and Transplant)

  • Vanja Karamatic Crew

    (International Blood Group Reference Laboratory, NHS Blood and Transplant)

  • Louise Tilley

    (International Blood Group Reference Laboratory, NHS Blood and Transplant)

  • Carole A. Green

    (Bristol Institute for Transfusion Sciences, NHS Blood and Transplant and NIHR Blood and Transplant Unit in Red Cell Products, University of Bristol)

  • Chwen Ling Tay

    (International Blood Group Reference Laboratory, NHS Blood and Transplant)

  • Rebecca E. Griffiths

    (Bristol Institute for Transfusion Sciences, NHS Blood and Transplant and NIHR Blood and Transplant Unit in Red Cell Products, University of Bristol)

  • Belinda K. Singleton

    (Bristol Institute for Transfusion Sciences, NHS Blood and Transplant and NIHR Blood and Transplant Unit in Red Cell Products, University of Bristol)

  • Frances Spring

    (Bristol Institute for Transfusion Sciences, NHS Blood and Transplant and NIHR Blood and Transplant Unit in Red Cell Products, University of Bristol)

  • Piers Walser

    (International Blood Group Reference Laboratory, NHS Blood and Transplant)

  • Abdul Ghani Alattar

    (Division of Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University)

  • Benjamin Jones

    (International Blood Group Reference Laboratory, NHS Blood and Transplant)

  • Rosalind Laundy

    (International Blood Group Reference Laboratory, NHS Blood and Transplant)

  • Jill R. Storry

    (Division of Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University
    Department of Clinical Immunology and Transfusion Medicine, Office of Medical Services)

  • Mattias Möller

    (Division of Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University)

  • Lorna Wall

    (Reference Laboratory, New Zealand Blood Service)

  • Richard Charlewood

    (Reference Laboratory, New Zealand Blood Service)

  • Connie M. Westhoff

    (New York Blood Centre)

  • Christine Lomas-Francis

    (New York Blood Centre)

  • Vered Yahalom

    (Magen David Adom, National Blood Services)

  • Ute Feick

    (Deutsches Rotes Kreuz, Blood Donor Service, Institute Bad Kreuznach)

  • Axel Seltsam

    (German Red Cross Blood Service NSTOB, Institute Springe)

  • Beate Mayer

    (Institute of Transfusion Medicine, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health)

  • Martin L. Olsson

    (Division of Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University
    Department of Clinical Immunology and Transfusion Medicine, Office of Medical Services)

  • David J. Anstee

    (Bristol Institute for Transfusion Sciences, NHS Blood and Transplant and NIHR Blood and Transplant Unit in Red Cell Products, University of Bristol)

Abstract

The clinically important MAM blood group antigen is present on haematopoietic cells of all humans except rare MAM-negative individuals. Its molecular basis is unknown. By whole-exome sequencing we identify EMP3, encoding epithelial membrane protein 3 (EMP3), as a candidate gene, then demonstrate inactivating mutations in ten known MAM-negative individuals. We show that EMP3, a purported tumour suppressor in various solid tumours, is expressed in erythroid cells. Disruption of EMP3 by CRISPR/Cas9 gene editing in an immortalised human erythroid cell line (BEL-A2) abolishes MAM expression. We find EMP3 to associate with, and stabilise, CD44 in the plasma membrane. Furthermore, cultured erythroid progenitor cells from MAM-negative individuals show markedly increased proliferation and higher reticulocyte yields, suggesting an important regulatory role for EMP3 in erythropoiesis and control of cell production. Our data establish MAM as a new blood group system and demonstrate an interaction of EMP3 with the cell surface signalling molecule CD44.

Suggested Citation

  • Nicole Thornton & Vanja Karamatic Crew & Louise Tilley & Carole A. Green & Chwen Ling Tay & Rebecca E. Griffiths & Belinda K. Singleton & Frances Spring & Piers Walser & Abdul Ghani Alattar & Benjamin, 2020. "Disruption of the tumour-associated EMP3 enhances erythroid proliferation and causes the MAM-negative phenotype," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17060-4
    DOI: 10.1038/s41467-020-17060-4
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