Abstract

Myeloid differentiation primary response 88 L265P was a functional mutant currently found in hematological tumors, especially occurred frequently in central nervous system lymphomas. The integrity of the blood brain barrier was critical to maintain the normal microenvironment in the brain. Blood brain barrier prevented neurotoxic plasma components, blood cells and pathogens from entering the brain. However, the molecular crosstalk between blood brain barrier and lymphoma cells required further investigation. In this study, human brain microvascular endothelial cells were used to simulate a blood-brain barrier model in vitro. It was found that the myeloid differentiation primary response 88 L265P lymphoma cells disrupted the function of brain microvascular endothelial cells barrier by the decrease of transepithelial electric resistance value, destruction of tight junction and increase of leukocyte adhesion molecules. These processes were achieved by activating NLR family pyrin domain containing 3 and nuclear factor kappa B pathway in brain microvascular endothelial cell. In addition, when Myeloid differentiation primary response 88 L265P lymphoma cells was treated with ibrutinib, there was no significant change on the permeability and integrity of the brain microvascular endothelial cell barrier.