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Distinct homotypic B-cell receptor interactions shape the outcome of chronic lymphocytic leukaemia

Author

Listed:
  • Claudia Minici

    (Biocrystallography Unit, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute
    Università Vita-Salute San Raffaele)

  • Maria Gounari

    (B-cell Neoplasia Unit, IRCCS San Raffaele Scientific Institute
    Present address: Institute of Applied Biosciences, Center for Research and Technology, 57001 Thessaloniki, Greece)

  • Rudolf Übelhart

    (Universitätsklinik Ulm)

  • Lydia Scarfò

    (Università Vita-Salute San Raffaele
    B-cell Neoplasia Unit, IRCCS San Raffaele Scientific Institute
    Strategic Research Program on CLL, IRCCS San Raffaele Scientific Institute)

  • Marcus Dühren-von Minden

    (Universitätsklinik Ulm)

  • Dunja Schneider

    (Centre for Biological Signaling Studies, Faculty of Biology, Albert-Ludwigs University of Freiburg)

  • Alpaslan Tasdogan

    (Universitätsklinik Ulm)

  • Alabbas Alkhatib

    (Centre for Biological Signaling Studies, Faculty of Biology, Albert-Ludwigs University of Freiburg)

  • Andreas Agathangelidis

    (B-cell Neoplasia Unit, IRCCS San Raffaele Scientific Institute)

  • Stavroula Ntoufa

    (Institute of Applied Biosciences, Center for Research and Technology)

  • Nicholas Chiorazzi

    (The Feinstein Institute for Medical Research)

  • Hassan Jumaa

    (Universitätsklinik Ulm)

  • Kostas Stamatopoulos

    (Institute of Applied Biosciences, Center for Research and Technology
    Genetics and Pathology, Uppsala University)

  • Paolo Ghia

    (Università Vita-Salute San Raffaele
    B-cell Neoplasia Unit, IRCCS San Raffaele Scientific Institute
    Strategic Research Program on CLL, IRCCS San Raffaele Scientific Institute)

  • Massimo Degano

    (Biocrystallography Unit, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute)

Abstract

Cell-autonomous B-cell receptor (BcR)-mediated signalling is a hallmark feature of the neoplastic B lymphocytes in chronic lymphocytic leukaemia (CLL). Here we elucidate the structural basis of autonomous activation of CLL B cells, showing that BcR immunoglobulins initiate intracellular signalling through homotypic interactions between epitopes that are specific for each subgroup of patients with homogeneous clinicobiological profiles. The molecular details of the BcR–BcR interactions apparently dictate the clinical course of disease, with stronger affinities and longer half-lives in indolent cases, and weaker, short-lived contacts mediating the aggressive ones. The diversity of homotypic BcR contacts leading to cell-autonomous signalling reconciles the existence of a shared pathogenic mechanism with the biological and clinical heterogeneity of CLL and offers opportunities for innovative treatment strategies.

Suggested Citation

  • Claudia Minici & Maria Gounari & Rudolf Übelhart & Lydia Scarfò & Marcus Dühren-von Minden & Dunja Schneider & Alpaslan Tasdogan & Alabbas Alkhatib & Andreas Agathangelidis & Stavroula Ntoufa & Nichol, 2017. "Distinct homotypic B-cell receptor interactions shape the outcome of chronic lymphocytic leukaemia," Nature Communications, Nature, vol. 8(1), pages 1-12, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15746
    DOI: 10.1038/ncomms15746
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    Cited by:

    1. Florian Märkl & Christoph Schultheiß & Murtaza Ali & Shih-Shih Chen & Marina Zintchenko & Lukas Egli & Juliane Mietz & Obinna Chijioke & Lisa Paschold & Sebastijan Spajic & Anne Holtermann & Janina Dö, 2024. "Mutation-specific CAR T cells as precision therapy for IGLV3-21R110 expressing high-risk chronic lymphocytic leukemia," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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