Dottorato in INNOVATION IN IMMUNO-MEDIATED AND HEMATOLOGICAL DISORDERS

Titolo della tesi: ROLE OF SIALYLATION IN CRONIC LYMPHOCYTIC LEUKEMIA AND OTHER HEMATOLOGICAL MALIGNANCIES

Sialylation is a type of post-translational modification consisting in the terminal addition of sialic acid to underlying glycans. It plays a significant role in various biological processes, including immune regulation and cell adhesion. The presence of sialylated structures on adhesion molecules, such as integrins and selectin ligands, plays an essential part in facilitating the interactions between cancer cells and the tumor microenvironment (TME). These interactions are responsible for the metastatic seeding in target organs and the evasion of immune attack by cancer cells. Chronic lymphocytic leukemia (CLL) is a type of malignancy that affects B-cells and is heavily influenced by the microenvironment of the lymph nodes (LNs) and bone marrow (BM). Migration and homing of CLL cells into these protective niches is fundamental for CLL development, progression, and resistance to therapy. The interaction with the TME is crucial for the pathogenesis of various hematological diseases, including multiple myeloma (MM), a neoplastic disorder characterized by the proliferation of abnormal plasma cells (PCs) within the BM. The present thesis aims at investigating the role of sialylation in the mechanisms of migration, homing, and immune evasion in CLL and MM. In order to develop innovative therapeutic approaches, it is essential to acquire a comprehensive understanding of the complex biological mechanisms underlying the pathophysiology of these malignancies.