Investigating the origins and pathogenesis of anaplastic large cell lymphoma

间变性大细胞淋巴瘤的起源和发病机制的研究

• 批准号: 2620297
• 金额: --
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2620297
• 关键词: Investigating; origins; pathogenesis; anaplastic; large

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.

间变性大细胞淋巴瘤 (ALCL) 是一种侵袭性外周 T 细胞非霍奇金淋巴瘤，通常以表达 CD30 且缺乏功能性 T 细胞受体 (TCR) 为特征。 ALCL 可分为四种亚型，包括系统性/淋巴结间变性淋巴瘤激酶 (ALK)+ 和 ALK- ALCL、皮肤 ALCL 和乳房植入物相关 ALCL (BIA-ALCL)。由于证据相互矛盾，ALCL 的起源和发病机制在很大程度上尚不清楚。特纳实验室之前的工作表明 ALK+ ALCL 的胸腺起源，外围的继发事件触发全面的恶性肿瘤。进一步的研究表明，这种继发事件可能涉及某种抗原刺激，从而导致 TCR 下调并促进 ALCL 进展。有趣的是，BIA-ALCL 也被认为是由存在于纹理乳房植入物表面的慢性抗原刺激引起的。在这个项目中，我们建议研究 ALCL 发生的原因和方式，特别关注阐明抗原刺激的性质以及这如何与功能性 TCR 的丧失和 ALCL 的后续发展相关。希望这项工作将有助于合理设计新的和/或改进的 ALCL 治疗策略。