Researchers Identify Enzyme as New Target for Treating Classical Hodgkin’s Lymphoma

Researchers Identify Enzyme as New Target for Treating Classical Hodgkin’s Lymphoma
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An enzyme called monoamine oxidase-A (MAO-A) contributes to the growth of classical Hodgkin’s lymphoma cells but not other lymphoma cells, a study reports.

It also indicated that a combination of standard Hodgkin’s therapies and compounds that inhibit the enzyme could improve treatment of the disease.

The study, “Monoamine oxidase A is highly expressed in classical Hodgkin lymphoma,” was published in The Journal of Pathology.

MAO-A plays a role in the functioning of mitochondria, cell components that generate energy. It has been associated with several psychiatric disorders, including antisocial behavior, anxiety, and autism. Recent studies have suggested that it also takes part in cancer development by promoting the activation of pro-tumor signaling pathways.

A research team led by Jean C. Shih, a professor at the University of Southern California, decided to see if MAO-A is involved in the development of classical Hodgkin’s and other lymphomas. Shih is director of the USC-Taiwan Center for Translational Research at USC’s School of Pharmacy.

The team checked the enzyme’s levels in 241 tissue samples from classical Hodgkin’s lymphoma patients, 169 samples from non-Hodgkin’s lymphoma cases, and, as a control, seven healthy tissue samples.

They found high levels of MAO-A in Hodgkin Reed-Sternberg cells, the malignant cell type that defines classical Hodgkin’s lymphoma. They failed to find the enzyme in samples from non-Hodgkin’s lymphoma patients and healthy controls. This suggested that MAO-A plays a role specifically in the development of classical Hodgkin’s lymphoma.

Indeed, when the team inhibited the enzyme’s activity in Hodgkin’s lymphoma, the cancer grew at a slower pace. In contrast, increasing the levels of MAO-A in Hodgkin’s lymphoma cells enhanced their proliferation.

While MAO-A inhibitors reduced the growth of classical Hodgkin’s lymphoma, the treatment was more effective when combined with a standard of care chemotherapy known as ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine). This suggested that MAO-A inhibitors could be combined with standard therapies to improve Hodgkin’s lymphoma patients’ outcomes.

“Our long-term goal is to better understand the molecular basis of cancer progression and provide insights on developing better diagnostic tools and treatment for cancer patients, to reduce their suffering,” Shih said in a university news release written by Michele Keller. “We hope these findings will bring new hope to patients and their families.”

The bottom line was that the findings added new knowledge on the biology of lymphoma subtypes, and identified MAO-A as a potential diagnostic marker for lymphomas that are difficult to recognize and treat.

USC said the Daniel Tsai Family Fund and the National Institutes of Health supported the study.

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