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Type of publication: Journal Article
Type of document: Full Paper

Year: 2016

Authors: Malcolm, TI; Villarese, P; Fairbairn, CJ; Lamant, L; Trinquand, A; Hook, CE; Burke, GA; Brugières, L; Hughes, K; Payet, D; Merkel, O; Schiefer, AI; Ashankyty, I; Mian, S; Wasik, M; Turner, M; Kenner, L; Asnafi, V; Macintyre, E; Turner, SD

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

Source: Nat Commun. 2016; 7:10087

Authors Vetmeduni Vienna:

Kenner Lukas

Vetmed Research Units
Institute of Pathology, Pathology of Laboratory Animals

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.

Keywords Pubmed: Adult
CD4 Antigensmetabolism
Cell Line, Tumor
Disease Models, Animal
Flow Cytometry
Gene Rearrangement, T-Lymphocyte
Genes, RAG-1genetics
Genes, T-Cell Receptor alpha
Genes, T-Cell Receptor beta
Jurkat Cells
Lymphoma, Large-Cell, Anaplasticmetabolism
Mice, Transgenic
Protein-Tyrosine Kinasesmetabolism
Receptor, Notch1metabolism
Receptors, Antigen, T-Cellmetabolism
Receptors, Antigen, T-Cell, alpha-betageneticsmetabolism
Reverse Transcriptase Polymerase Chain Reaction
Thymus Glandcytology

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