Challenging perspectives on the cellular origins of lymphoma.
Both B and T lymphocytes have signature traits that set them apart from other cell types. They actively and repeatedly rearrange their DNA in order to produce a unique and functional antigen receptor, they have potential for massive clonal expansion upon encountering antigen via this receptor or its precursor, and they have the capacity to be extremely long lived as 'memory' cells. All three of these traits are fundamental to their ability to function as the adaptive immune response to infectious agents, but concurrently render these cells vulnerable to transformation. Thus, it is classically considered that lymphomas arise at a relatively late stage in a lymphocyte's development during the process of modifying diversity within antigen receptors, and when the cell is capable of responding to stimulus via its receptor. Attempts to understand the aetiology of lymphoma have reinforced this notion, as the most notable advances to date have shown chronic stimulation of the antigen receptor by infectious agents or self-antigens to be key drivers of these diseases. Despite this, there is still uncertainty about the cell of origin in some lymphomas, and increasing evidence that a subset arises in a more immature cell. Specifically, a recent study indicates that T-cell lymphoma, in particular nucleophosmin-anaplastic lymphoma kinase-driven anaplastic large cell lymphoma, may originate in T-cell progenitors in the thymus.
Division of Molecular Histopathology, Department of Pathology, University of Cambridge, Lab Block Level 3, Box 231, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
Tim I M
TI
Malcolm
Department of Haematology, University of Cambridge, Cambridge, UK.
Daniel J
DJ
Hodson
Hematology and INSERM1151, Institut Necker-Enfants Malades, Université Sorbonne Paris Cité at Descartes and Assistance Publique-Hôpitaux de Paris, Paris 75743 Cedex 15, France.
Elizabeth A
EA
Macintyre
Division of Molecular Histopathology, Department of Pathology, University of Cambridge, Lab Block Level 3, Box 231, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK sdt36@cam.ac.uk.
Suzanne D
http://orcid.org/0000-0002-8439-4507
SD
Turner
T cell; anaplastic large cell lymphoma; lymphomagenesis
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