High-dose Vitamin C May Be Effective Against Lymphoma, Other Blood Cancers, Say Researchers

High-dose Vitamin C May Be Effective Against Lymphoma, Other Blood Cancers, Say Researchers

Vitamin C boosts processes that allow faulty blood stem cells to die instead of multiplying uncontrollably to cause lymphoma or other blood cancers, say researchers at NYU Langone Health‘s Perlmutter Cancer Center.

Their study, “Restoration of TET2 Function Blocks Aberrant Self-Renewal and Leukemia Progression,” appeared in the journal Cell. It showed that vitamin C counteracts the effects of a malfunctioning enzyme, called TET2, present in many lymphoma and leukemia patients.

“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,” Dr. Benjamin G. Neel, a co-senior study author and professor at the Perlmutter Cancer Center’s Department of Medicine, said in a press release.

The study used a genetically engineered mouse model of mutated TET2 to study the impact of vitamin C on blood stem cell maturation and cancer.

The enzyme is involved in what researchers call epigenetic regulation of gene activity. Epigenetics refers to the use of chemical flags, directly attached to DNA, to determine if a gene is active or not.

When chemical methyl groups are attached to the DNA of a gene, the protein-making machinery cannot reading the gene. TET2 triggers molecular changes that allow the removal of these methyl groups on genes that determine the maturation of blood stem cells.

When TET2 is mutated, stem cells in the bone marrow fail to mature into white blood cells. But they also fail to self-destruct, which they normally do when not needed. Instead, they divide and swamp the blood with abnormal immature blood stem cells to cause cancer.

Researchers, however, knew that TET2 mutations only affect only one of two gene copies. Previous work had shown that vitamin C could stimulate the activity of TET2. Now, they figured that high levels of vitamin C — given as intravenous infusions — might boost the activity of the remaining TET2 gene to restore normal processes that allow blood stem cells to mature or die.

Their experiments showed that, indeed, this was the case. Vitamin C helped remove methyl groups, activating crucial genes. They also showed that treatment with the vitamin increased cancer cells’ sensitivity to PARP inhibitors, suggesting that combining high-dose vitamin C and a PARP inhibitor might improve treatment outcomes.

“Interestingly, we also found that vitamin C treatment had an effect on leukemic stem cells that resembled damage to their DNA,” said the study’s first author, Luisa Cimmino, an assistant professor at NYU Langone Health’s Department of Pathology. “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.”

PARP inhibitors are now in clinical development for several types of lymphoma as well as other blood cancers.

“Our team is working to systematically identify genetic changes that contribute to risk for leukemia in significant groups of patients,” said professor Iannis Aifantis, who led the research along with Neel. “This study adds the targeting of abnormal TET2-driven DNA demethylation to our list of potential new treatment approaches.”

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Magdalena is a writer with a passion for bridging the gap between the people performing research, and those who want or need to understand it. She writes about medical science and drug discovery. She holds an MS in Pharmaceutical Bioscience and a PhD — spanning the fields of psychiatry, immunology, and neuropharmacology — from Karolinska Institutet in Sweden.

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