<p>Biomarkers Reflecting The Destruction Of The Blood-Brain Barrier Are Valuable In Predicting The Risk Of Lymphomas With Central Nervous System Involvement</p>

Abstract

ObjectiveWe aimed to identify the biomarkers in cerebrospinal fluid (CSF) that facilitate the diagnosis of lymphomas with central nervous system (CNS) involvement.MethodsFour cases of non-Hodgkin’s lymphoma (NHL) patients with/without CNS involvement were enrolled respectively, and non-CNS tumor patients (n=3) were selected to be the controls. Lab biomarkers, cytokines, and tight junction proteins (TJs) in CSF and serum were measured.ResultsWhen comparing the CNS to non-CNS group, cytokine including MMP-9 (15.24 vs 0.36 ng/mL), CCL-2 (1922.04 vs 490.68 pg/mL), and sVCAM-1 (61.36 vs 9.00 pg/mL), TJs including OCLN (6.68 vs 2.59 pg/mL), and ZO-1 (710.04 vs 182.98 pg/mL) in CSF were significantly higher in lymphomas patients with CNS involvement than those without CNS involvement. However, serum biomarkers were not significantly elevated. Contrary to the major findings, all conventional biomarkers and MRI results showed no significant change.ConclusionCSF biomarkers affecting BBB disruption are valuable in mirroring the risk of lymphoma CNS metastasis. Further study with a larger sample size is needed to verify these biomarkers in predicting lymphoma CNS involvement.

New Insights into Diffuse Large B-Cell Lymphoma Pathobiology

“…Moreover, the initial observation that the expression level of the adhesion molecules by the malignant lymphoma cells can predict disease outcome in extranodal DLBCL [ 128 ] prompted further investigation, especially in peculiar clinical disease phenotypes, such as DLBCLs involving the central nervous system (CNS) [ 128 ]. Remarkably, CNS spreading represents a paradigmatic extranodal localization with peculiar pathobiology involving adhesion molecule deregulated expression [ 129 ] and hyperactivation of the angiogenesis fueling pathway [ 130 ] along with a truncal genomic signature [ 131 ], which can contribute to drug sensitivity and resistance [ 132 , 133 , 134 ], as in other malignancies [ 135 , 136 , 137 ]. Therefore, given that the aberrant expression of adhesion molecules on bone marrow endothelial cells of patients with lymphoid and myeloid neoplasia was also discovered to predict poor clinical outcome [ 138 , 139 , 140 , 141 ], it is tempting to speculate a vicious cycle in DLBCL by paralleling the neoplastic cell behavior [ 128 ], whereby the described molecular signature [ 36 , 142 ] has more interactions among themselves than what would be expected for a random set of gene-encoding proteins drawn from the genome [ 143 ].…”

New insights in Diffuse Large B Cell Lymphoma Pathobiology

“…Remarkably, CNS spreading represents a paradigmatic extranodal localization with peculiar pathobiology involving adhesion-molecule deregulated expression [129], hyperactivation of angiogenesis fueling pathway [130] along with truncal genomic signature [131] that can contribute to drug sensitivity and resistance [132][133][134], as in other malignancies [135][136][137]. Therefore, given that the aberrant expression of adhesion molecules also on bone marrow endothelial cells of patients with lymphoid and myeloid neoplasia has been discovered to predict poor clinical outcome [138][139][140][141], it is tempting to speculate a vicious cycle in DLBCL by paralleling the neoplastic cells behavior [128] and that the described molecular signature [36,142] have more interactions among themselves than what would be expected for a random set of gene encoding proteins drawn from the genome [143].…”