Monoamine Oxidase a (MAO A) Is Expressed Selectively in Reed-Sternberg Cells of Classical Hodgkin Lymphoma

Monoamine oxidase A (MAO A) is a mitochondrial enzyme, which catalyzes oxidative deamination of neurotransmitters or dietary amines and produces H₂O₂.  Recent work indicates that MAO A is overexpressed in prostate cancer.  Inhibiting its activity suppresses tumorigenesis and metastasis. In this study, we showed that Hodgkin lymphoma (HL)-derived L1236 cells express high MAO A activity, while other human lymphoma cell lines examined, including both Hodgkin and non-Hodgkin lymphoma, do not express MAO A.  We also analyzed MAO A expression by immunohistochemistry in formalin-fixed paraffin-embedded classical Hodgkin (n=88), nodular lymphocyte predominant Hodgkin (n=8) and non-Hodgkin lymphoma (diffuse large B-cell lymphoma, n=54; follicular, n=33; Burkitt lymphoma, n= 19; mantle cell lymphoma, n= 13).  We found that 60% of the classical Hodgkin lymphoma (cHL) cases demonstrated at least some MAO A expression by the neoplastic Reed-Sternberg cells and 30% of the tumors show strong/uniform expression. In contrast, no MAO A activity was seen in normal lymphoid tissue, nodular lymphocyte predominant Hodgkin lymphoma or non-Hodgkin lymphomas. The MAO inhibitor clorgyline inhibited MAO A activity (IC₅₀ of 8.3×10^-9 M) and was cytotoxic (IC₅₀ of 30 μM) to L1236 cells.  In addition, clorgyline reduced the cell proliferation, colony formation, and invasion of L1236 cells in vitro.   Taken together, we have shown for the first time that MAO A is expressed selectively in Reed-Sternberg cells of cHL.  Our results suggest that MAO A may be a biomarker for classical Hodgkin lymphoma Reed-Sternberg cells and may provide biological insights as well as a potential therapeutic target.