Vitamin C may "tell" faulty stem cells in the bone marrow to mature and die normally, instead of multiplying to cause blood cancers. This is the finding of a study led by researchers from Perlmutter Cancer Center at NYU Langone Health, and published online August 17 in the journal Cell.

Certain genetic changes are known to reduce the ability of an enzyme called TET2 to encourage stem cells to become mature blood cells, which eventually die, in many patients with certain kinds of leukemia, say the authors. The new study found that vitamin C activated TET2 function in mice engineered to be deficient in the enzyme.

"We're excited by the prospect that high–dose vitamin C might become a safe treatment for blood diseases caused by TET2–deficient leukemia stem cells, most likely in combination with other targeted therapies," says corresponding study author Benjamin G. Neel, MD, PhD, professor in the Department of Medicine and director of the Perlmutter Cancer Center.

Mutations that reduce TET2 function are found in 10 percent of patients with acute myeloid leukemia (AML), 30 percent of those with a form of pre–leukemia called myelodysplastic syndrome, and in nearly 50 percent of patients with chronic myelomonocytic leukemia. Such cancers cause anemia, infection risk, and bleeding as abnormal stem cells multiply in the bone marrow until they interfere with blood cell production, with the number of cases increasing as the population ages.

Along with these diseases, new tests suggest that about 2.5 percent of all U.S. cancer patients – or about 42,500 new patients each year – may develop TET2 mutations, including some with lymphomas and solid tumors, say the authors. "Interestingly, we also found that vitamin C treatment had an effect on leukemic stem cells that resembled damage to their DNA," says first study author Luisa Cimmino, PhD, an assistant professor in the Department of Pathology at NYU Langone Health. "For this reason, we decided to combine vitamin C with a PARP inhibitor, a drug type known to cause cancer cell death by blocking the repair of DNA damage, and already approved for treating certain patients with ovarian cancer."

Researchers found that the combination had an enhanced effect on leukemia stem cells, further shifting them from self–renewal back toward maturity and cell death. The results also suggest that vitamin C might drive leukemic stem cells without TET2 mutations toward death, says Cimmino, given that it turns up any TET2 activity normally in place.

"Our team is working to systematically identify genetic changes that contribute to risk for leukemia in significant groups of patients," says corresponding author Iannis Aifantis, PhD, professor and chair of the Department of Pathology at NYU Langone Health. "This study adds the targeting of abnormal TET2–driven DNA demethylation to our list of potential new treatment approaches."