Grant: Project Grant

Lymphoma, which represents the 5th most common malignancy, is a type of cancer involving cells of the immune system, called lymphocytes. Lymphomas which specifically develop in the chest cavity ('anterior mediastinum') with bulky tumour masses, collectively termed as mediastinal lymphomas, share common gene mutations and certain patient characteristics such as disease occurrence at a young age; however, little is known about how mediastinal lymphomas develop and why therapies fail to eliminate the cancer in some patients. Although modern treatments have led to better overall survival for most lymphoma patients, disease-related mortality is still high when disease progression or relapse occurs. Importantly, as mediastinal lymphomas arise at a relatively young age, implementation of more effective and less-toxic therapies is highly desirable. Our group has already performed numerous genetic studies which resulted in better understanding of the biology of mediastinal lymphomas thus building a foundation for further study. With this proposal, we aim to further improve our understanding about how specific gene mutations contribute to the development and persistence of the tumour in mediastinal lymphomas. In particular, we will explore the influence of gene mutations in the CSF2RB gene that is important for cell signaling in lymphocytes (mediated by cytokines). Of note, these mutations were identified specifically in mediastinal lymphomas but not in other main lymphomas. We will also study how lymphoma cells with CSF2RB mutations depend on the interactions with non-malignant cells that constitute the tumor microenvironment (TME) for their growth and survival. Our study is very important to identify novel drug targets in both lymphoma cells and their TME and to guide physicians to select the best therapy for individual patients. We anticipate that our study will lead to higher cure rates and fewer treatment-related side effects for patients with mediastinal lymphomas.