Investigating the origins and pathogenesis of anaplastic large cell lymphoma

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Anaplastic large cell lymphoma (ALCL) is an aggressive form of peripheral T cell non-Hodgkin lymphoma, often characterised by the expression of CD30 and the absence of a functional T cell receptor (TCR). ALCL can be divided into four subtypes, including systemic/nodal anaplastic lymphoma kinase (ALK)+ and ALK- ALCL, cutaneous ALCL and breast implant associated ALCL (BIA-ALCL). Due to conflicting evidence, the origin and pathogenesis of ALCL is largely unknown. Previous work by the Turner lab has suggested a thymic origin for ALK+ ALCL, with secondary events in the periphery triggering full blown malignancy. Further work suggested that this secondary event could involve some sort of antigenic stimulus which leads to the downregulation of the TCR and enables ALCL progression. Interestingly, BIA-ALCL is also thought to be caused by a chronic antigenic stimulus, present on the surface of textured breast implants. In this project, we propose to investigate why and how ALCL develops, with specific focus on elucidating the nature of the antigenic stimulus and how this may be linked to the loss of a functional TCR and the subsequent development of ALCL. It is hoped that this work will facilitate the rational design of new and/or improved therapeutic strategies for ALCL.