Study sheds light on enzyme's role in driving lymphoma growth

MSN highlighted a study led by University of Cincinnati Cancer Center researchers that sheds new light on the mechanisms by which a major oncogene promotes and sustains lymphoma development and progression, paving the way for novel targeted therapies.

The research, led by first author Austin C. MacMillan and senior author Tom Cunningham, was published May 29 in the journal Redox Biology.

The Cunningham lab focuses on an oncogene called MYC that “turbocharges” the metabolism of cancer cells to fuel their aggressive growth and proliferation. The team examined the role of an enzyme called phosphoribosyl pyrophosphate synthetase (PRPS) that is present in lymphoma cells in two forms: PRPS1 and PRPS2. Using CRISPR gene editing technology, the team knocked out either form of the enzyme in lymphoma cell line models.

The researchers found that PRPS1 and PRPS2 have different activities but work together in the same biochemical complex, with PRPS2 increased and more active in lymphoma cells where MYC is overexpressed.

“The PRPS enzymes and the PRPS complex have a cell-wide effect on redox homeostasis,” said MacMillan, a doctoral cancer biology student in Cunningham’s lab. “The many buffering mechanisms in place to regulate redox homeostasis make it very uncommon to find that the difference in catalyzation of a single biochemical reaction produces such a measurable change in the cell’s global redox state, so that was a major surprise.”

“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 overall cellular redox state,” Cunningham added. “Having the molecular tools at our disposal to harness that is a really powerful bit of knowledge that we can use in the future.”

Read the MSN article.

Featured photo at top of a researcher pipetting samples in the Cunningham lab. Photo/Andrew Higley/UC Marketing + Lab.