Monoamine oxidase A is highly expressed in classical Hodgkin lymphoma

• Published in: The Journal of pathology 2017-10, Vol.243 (2), p.220-229
• Main Authors: Li, Pei Chuan, Siddiqi, Imran N, Mottok, Anja, Loo, Eric Y, Wu, Chieh Hsi, Cozen, Wendy, Steidl, Christian, Shih, Jean Chen
• Format: Article
• Language: English
• Subjects: Amine oxidase (flavin-containing); Amines; B-cell lymphoma; Bleomycin; Cell Line, Tumor; classical Hodgkin lymphoma; Clorgyline - pharmacology; Combined treatment; Dacarbazine; Deamination; Doxorubicin; Epstein-Barr virus; Epstein-Barr Virus Infections - enzymology; Female; Hodgkin Disease - enzymology; Hodgkin Reed–Sternberg (HRS) cells; Humans; Hydrogen peroxide; Immunohistochemistry; Lymphocytes B; Lymphoid tissue; Lymphoma; Male; Middle Aged; Mitochondria; Monoamine Oxidase - metabolism; monoamine oxidase A (MAOA); Monoamine Oxidase Inhibitors - pharmacology; Neurotransmitters; Paraffin; Prostate cancer; Reed-Sternberg Cells - metabolism; Tissues; Tumor cell lines; Vinblastine
• ISSN: 0022-3417; 1096-9896
• DOI: 10.1002/path.4944

Monoamine oxidase A (MAOA) is a mitochondrial enzyme that catalyzes oxidative deamination of neurotransmitters and dietary amines and produces H2O2. It facilitates the progression of gliomas and prostate cancer, but its expression and functional relevance have not been studied in lymphoma. Here, we evaluated MAOA in 427 cases of Hodgkin and non‐Hodgkin lymphoma and in a spectrum of reactive lymphoid tissues by immunohistochemistry on formalin‐fixed, paraffin‐embedded specimens. MAOA was expressed by Hodgkin Reed–Sternberg (HRS) cells in the majority of classical Hodgkin lymphomas (cHLs) (181/241; 75%), with 34.8% showing strong expression. Weak MAOA was also noted in a minority of primary mediastinal large B‐cell lymphomas (8/47; 17%) and in a mediastinal gray‐zone lymphoma. In contrast, no MAOA was found in non‐neoplastic lymphoid tissues, nodular lymphocyte‐predominant Hodgkin lymphoma (NLPHL; 0/8) or any other non‐Hodgkin lymphomas studied (0/123). MAOA was more common in Epstein–Barr virus (EBV)‐negative compared to EBV‐positive cHL (p < 0.0001) and was especially prevalent in the EBV‐negative nodular sclerosing subtype. Similar to primary human lymphoma specimens, most cHL‐derived cell lines displayed MAOA activity, whereas non‐Hodgkin‐lymphoma‐derived cell lines did not. The MAOA inhibitor clorgyline reduced the growth of L1236 cells and U‐HO1 cells, and shRNA knockdown of MAOA reduced the growth of L1236 cells. Conversely, ectopic overexpression of MAOA increased the growth of MAOA‐negative HDLM2 cells. Combined treatment with clorgyline and ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) was more effective in reducing cell growth than either regimen alone. In summary, MAOA is highly expressed in cHL and may reflect the distinct biology of this lymphoma. Further studies on the potential utility of MAOA as a diagnostic marker and therapeutic target are warranted. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.