Vitamin C Could be Used to Tell Blood Cancer Stem Cells to Die

Vitamin C Could be Used to Tell Blood Cancer Stem Cells to Die

Researchers at the Perlmutter Cancer Center at NYU Langone Health have found high doses of vitamin C have potential to be used as a treatment for certain types of leukemia.

Certain blood cancers involve genetic mutations that reduce the function of an enzyme called TET2 (Tet methylcytosine dioxygenase 2). TET2 encourages stem cells in the bone marrow to form mature blood cells. Instead, reduced TET2 activity results in stem cells multiplying, which interferes with blood cell production.

The researchers explain that isocitrate dehydrogenase-1 gene (IDH1) mutations are a driver in acute myeloid leukemia (AML), but point out that the exact mechanism is not well understood. It is believed that IDH1 mutants inhibit TET2 by altering DNA methylation, encouraging the stem cells to self-renew and multiply.

These genetic mutations are present in approximately 10% of patients with AML, 30% of patients with myelodysplastic syndrome and almost 50 percent of patients with chronic myelomonocytic leukemia. TET2 mutations are also associated with some lymphomas and solid tumors according to the researchers.

The team discovered that mice who are deficient in the TET2 enzyme had TET2 function activated when they were administered with high doses of vitamin C, leading the researchers to believe that Vitamin C could be used as a treatment for certain blood cancers, and certainly beneficial alongside other traditional therapies.

In addition to restoring TET2 activity, vitamin C also suppressed the growth of leukemia cancer stem cells. Vitamin C appeared to cause damage to the cancer stem cells that resembled DNA damage. By combining vitamin C treatment with a PARP inhibitor, which blocks the repair of DNA, the effect on the leukemia stem cells was enhanced, stopping self-renewal and encouraging maturity and cell death.

PARP inhibitors are already an approved treatment for ovarian cancer. Combination with high doses of intravenous vitamin C could serve as a potential new treatment approach for blood diseases caused by TET2-deficient leukemia stem cells.

The research – Mutant IDH1 Downregulates ATM and Alters DNA Repair and Sensitivity to DNA Damage Independent of TET2 – was published today in the journal Cell.

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