Study Sheds Light on Enzyme’s Role in Driving Lymphoma Growth

Updated May 30, 2025

Cincinnati, OH—Researchers at the University of Cincinnati Cancer Center have uncovered new details about how a major oncogene supports lymphoma development, perhaps leading to new targeted therapies. The study, published in Redox Biology, focuses on the mechanisms ‍by which⁢ the MYC oncogene promotes aggressive growth in lymphoma cells.

tom Cunningham, an associate professor at UC’s College of ‍Medicine, explained that‍ MYC boosts cancer cell metabolism. While ⁣many pathways activated⁤ by MYC are known, the coordination ⁣of these processes in⁤ driving cancer remains unclear. The Cunningham lab’s research ⁣highlights the importance of redox homeostasis—the balance⁣ between oxidation and reduction—in cancer cells.

According to Cunningham, maintaining redox balance⁣ is crucial for cell survival. Too much oxidative or reductive stress can damage cells, making the disruption of redox functions a potential strategy to weaken or‍ kill cancer cells. The team‍ investigated the role of phosphoribosyl pyrophosphate synthetase (PRPS), an‍ enzyme present ‍in ⁢two forms, PRPS1 and ‍PRPS2, within lymphoma cells.

using ‍CRISPR gene editing, the⁤ researchers eliminated each form of ‍the enzyme in lymphoma cell lines.⁣ They discovered that ⁤PRPS1 and PRPS2 have distinct activities but function together. ‍PRPS2 was found to be more‍ active in lymphoma ⁤cells with MYC overexpression. Austin macmillan, a doctoral student in cancer biology, noted that the PRPS⁢ complex significantly ‍affects redox⁤ homeostasis.

MacMillan emphasized the surprising finding that altering⁣ a single biochemical reaction could produce such a measurable change in the cell’s global redox state. Eliminating PRPS1 increased sensitivity to oxidative ⁢stress,while eliminating PRPS2 triggered reductive stress. The team⁣ concluded that MYC remodels the PRPS complex, offering a potential target for therapies.

“Disabling PRPS2 turns out to be one ‍of⁣ only a handful of loss of function strategies we know of that ⁤can induce reductive stress,”⁣ MacMillan said.

“There are so many checks and balances,so many ways of recalibrating ⁣that cellular redox state to keep it stable. Discovering that changing flux through the single ⁢PRPS enzyme can have such profound consequences on the overall cellular redox state,” Cunningham added.

What’s next

The study’s findings pave the way for preclinical testing to identify drugs ‍and pathways that can further disrupt the redox state of lymphoma cells. Cunningham’s team is currently developing and testing approaches to manipulate the⁤ PRPS ‍enzyme, potentially in combination with chemotherapies, to combat aggressive lymphomas overexpressing MYC.