Role of Galectin-9 in Chronic Lymphocytic Leukemia

Abstract

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western countries, characterized by the progressive accumulation of mature, functionally incompetent B lymphocytes. The immune microenvironment plays a pivotal role in CLL pathogenesis, influencing tumor cell survival and disease progression. Among immune-regulatory molecules, Galectin-9 (Gal-9) has emerged as a key immunomodulatory protein belonging to the β-galactoside–binding lectin family. It is known to interact with TIM-3 and other receptors, leading to T-cell exhaustion and apoptosis, thereby contributing to tumor immune evasion. Recent evidence suggests that Gal-9 may have dual roles in cancer biology, functioning either as an immune checkpoint ligand promoting tumor escape or as an apoptosis-inducing molecule depending on the cellular context. However, its exact role in the immunopathogenesis and clinical behavior of CLL remains incompletely defined.