Lab mouse
Preclinical research suggests high-dose vitamin C may be effective against TET2-mutant leukemias.
Investigators found that vitamin C mimics TET2 restoration, thereby suppressing leukemic colony formation, inhibiting leukemia progression in mice, and enhancing leukemia cells’ sensitivity to treatment with a PARP inhibitor.
“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,” said study author Benjamin G. Neel, MD, PhD, of NYU School of Medicine in New York, New York.
Dr Neel and his colleagues reported their findings in Cell.
Previous research had shown that vitamin C could stimulate the activity of TET2 as well as TET1 and TET3.
Because only 1 copy of the TET2 gene in each stem cell is usually affected in TET2-mutant blood diseases, the investigators hypothesized that high doses of vitamin C might reverse the effects of TET2 deficiency by turning up the action of the remaining functional gene.
Indeed, the team found that vitamin C had the same effect as restoring TET2 function genetically. By promoting DNA demethylation, high-dose vitamin C induced stem cells to mature and suppressed the growth of leukemic stem cells (LSCs) implanted in mice.
“Interestingly, we also found that vitamin C treatment had an effect on leukemic stem cells that resembled damage to their DNA,” said study author Luisa Cimmino, PhD, of NYU School of Medicine.
“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.”
The combination had an enhanced effect on LSCs, further shifting them from self-renewal back toward maturity and cell death.
Dr Cimmino said these results suggest vitamin C might also be effective against leukemias without TET2 mutations. As vitamin C turns up any TET2 activity normally in place, it might drive LSCs without TET2 mutations toward death as well.
