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Anaplastic large cell lymphoma arises in thymocytes and requires transient TCR expression for thymic egress

Author

Listed:
  • Tim I. M. Malcolm

    (University of Cambridge)

  • Patrick Villarese

    (Hematology and INSERM1151, Institut Necker-Enfants Malades, Université Sorbonne Paris Cité at Descartes and Assistance Publique-Hôpitaux de Paris, Paris 75743, France)

  • Camilla J. Fairbairn

    (University of Cambridge)

  • Laurence Lamant

    (Institut Universitaire de Cancérologie Oncopole)

  • Amélie Trinquand

    (Hematology and INSERM1151, Institut Necker-Enfants Malades, Université Sorbonne Paris Cité at Descartes and Assistance Publique-Hôpitaux de Paris, Paris 75743, France)

  • C. Elizabeth Hook

    (Addenbrooke’s Hospital)

  • G. A. Amos Burke

    (Addenbrooke’s Hospital)

  • Laurence Brugières

    (Gustave Roussy)

  • Katherine Hughes

    (University of Cambridge)

  • Dominique Payet

    (Centre d’Immunologie de Marseille Luminy (CIML), INSERM UMR1104, CNRS UMR7280, Aix-Marseille Université UM2)

  • Olaf Merkel

    (Clinical Institute of Pathology, Medical University of Vienna)

  • Ana-Iris Schiefer

    (Clinical Institute of Pathology, Medical University of Vienna)

  • Ibraheem Ashankyty

    (Molecular Diagnostics and Personalized Therapeutics Unit, College of Applied Medical Sciences University of Ha’il)

  • Shahid Mian

    (Molecular Diagnostics and Personalized Therapeutics Unit, College of Applied Medical Sciences University of Ha’il)

  • Mariusz Wasik

    (University of Pennsylvania)

  • Martin Turner

    (The Babraham Institute)

  • Lukas Kenner

    (Clinical Institute of Pathology, Medical University of Vienna
    Ludwig Boltzmann Institute for Cancer Research (LBI-CR)
    University of Veterinary Medicine Vienna)

  • Vahid Asnafi

    (Hematology and INSERM1151, Institut Necker-Enfants Malades, Université Sorbonne Paris Cité at Descartes and Assistance Publique-Hôpitaux de Paris, Paris 75743, France)

  • Elizabeth Macintyre

    (Hematology and INSERM1151, Institut Necker-Enfants Malades, Université Sorbonne Paris Cité at Descartes and Assistance Publique-Hôpitaux de Paris, Paris 75743, France)

  • Suzanne D. Turner

    (University of Cambridge)

Abstract

Anaplastic large cell lymphoma (ALCL) is a peripheral T-cell lymphoma presenting mostly in children and young adults. The natural progression of this disease is largely unknown as is the identity of its true cell of origin. Here we present a model of peripheral ALCL pathogenesis where the malignancy is initiated in early thymocytes, before T-cell receptor (TCR) β-rearrangement, which is bypassed in CD4/NPM–ALK transgenic mice following Notch1 expression. However, we find that a TCR is required for thymic egress and development of peripheral murine tumours, yet this TCR must be downregulated for T-cell lymphomagenesis. In keeping with this, clonal TCR rearrangements in human ALCL are predominantly in-frame, but often aberrant, with clonal TCRα but no comparable clonal TCRβ rearrangement, yielding events that would not normally be permissive for survival during thymic development. Children affected by ALCL may thus harbour thymic lymphoma‐initiating cells capable of seeding relapse after chemotherapy.

Suggested Citation

  • Tim I. M. Malcolm & Patrick Villarese & Camilla J. Fairbairn & Laurence Lamant & Amélie Trinquand & C. Elizabeth Hook & G. A. Amos Burke & Laurence Brugières & Katherine Hughes & Dominique Payet & Ola, 2016. "Anaplastic large cell lymphoma arises in thymocytes and requires transient TCR expression for thymic egress," Nature Communications, Nature, vol. 7(1), pages 1-12, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10087
    DOI: 10.1038/ncomms10087
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