Waldenström macroglobulinemia (WM) is a type of non-Hodgkin lymphoma associated with excessive immunoglobulin M (IgM) and bone marrow infiltration by lymphoplasmacytic cells. There is a dynamic oxygen gradient in the tumor microenvironment, leading to regions of hypoxia (1-3% O2 concentration). GLI1, GLI2 and GLI3 are members of the family of Kruppel-like factors with highly conserved Zinc finger DNA-binding domains in mammalian cells. We have previously shown that GLI2 modulates IgM secretion in WM. However, their expression during hypoxic conditions has not been investigated in WM. Here, we found that GLI1, GLI2 and GLI3 mRNA expression is induced under hypoxic conditions. However, only GLI1 protein was increased under similar conditions. We found that hypoxia promotes cell viability but there was no change in IgM secretion. We also found an induction in IL-2Rα (CD25) and IL-6Rα (gp80) under hypoxic conditions suggesting GLI proteins may regulate the expression of these cytokine receptors. Silencing GLI1 using RNAi reduces IL-2R α mRNA expression. Taken together, our studies show an induction in GLI1 mRNA and protein expression under hypoxic conditions in WM resulting in the regulation of IL-2Rα expression.
