Galectin-9 treatment is cytotoxic for B cell lymphoma by disrupting autophagy

Lisanne Koll¹Harm Jan Lourens¹Glenn Marsman¹Stan de Haan¹Toshiro Niki²Gerwin Huls¹Edwin Bremer¹Valerie R. Wiersma^1*

• ¹Department of Hematology, University Medical Center Groningen, Groningen, Netherlands
• ²Department of Immunology, Kagawa University, Takamatsu, Kagawa, Japan

The main cause of death for patients with non-Hodgkin lymphoma (NHL) remains therapy resistant relapses. Chemoresistance is commonly associated with apoptosis defects and upregulated autophagy. Therefore, novel therapeutic options that do not rely on apoptosis and target autophagy would be of interest to treat NHL. An agent that may fulfill these requirements is the glycan-binding protein Galectin-9 (Gal-9). Indeed, treatment with Gal-9 reduced total cell counts and cell viability of various B cell NHL cell lines, including diffuse large B cell lymphoma (DLBCL), mantle cell lymphoma (MCL), Burkitt's lymphoma (BL), and follicular lymphoma (FL). Gal-9-induced cell death was associated with the inhibition of autophagy, as demonstrated by the accumulation of LC3B-II and p62. In addition, Gal-9-sensitive cells expressed lower basal protein levels of LC3B-I. Furthermore, Gal-9 was cytotoxic for chemoresistant Sc-1 cells (Sc-1-RES), which were even more sensitive toward Gal-9 treatment than the parental cells (Sc-1-PAR). Thus, Gal-9 potently induced cell dead in B cell lymphoma cells by disrupting autophagy.