Dr. Weeks’ Comment: Vitamin C is an important help for people who have cancer. Dr. Levin claims that it “selectively kills cancer cells”. Here we have great data that it also helps with leukemia.
“… Treatment with vitamin C, ….. suppresses human leukemic colony formation and leukemia progression…. vitamin C treatment in leukemia cells enhances their sensitivity to PARP inhibition and could provide a safe and effective combination strategy to selectively target TET deficiency in cancer…”
Restoration of TET2 Function Blocks Aberrant Self-Renewal and Leukemia Progression
- •Tet2 restoration reverses aberrant self-renewal of Tet2-deficient cells
- •Tet2 restoration promotes DNA demethylation, differentiation, and cell death
- •Vitamin C treatment mimics Tet2 restoration to block leukemia progression
- •Vitamin C treatment in leukemia cells enhances their sensitivity to PARP inhibition
Loss-of-function mutations in TET2 occur frequently in patients with clonal hematopoiesis, myelodysplastic syndrome (MDS), and acute myeloid leukemia (AML) and are associated with a DNA hypermethylation phenotype. To determine the role of TET2 deficiency in leukemia stem cell maintenance, we generated a reversible transgenic RNAi mouse to model restoration of endogenous Tet2 expression. Tet2 restoration reverses aberrant hematopoietic stem and progenitor cell (HSPC) self-renewal in vitro and in vivo. Treatment with vitamin C, a co-factor of Fe2+ and α-KG-dependent dioxygenases, mimics TET2 restoration by enhancing 5-hydroxymethylcytosine formation in Tet2-deficient mouse HSPCs and suppresses human leukemic colony formation and leukemia progression of primary human leukemia PDXs. Vitamin C also drives DNA hypomethylation and expression of a TET2-dependent gene signature in human leukemia cell lines. Furthermore, TET-mediated DNA oxidation induced by vitamin C treatment in leukemia cells enhances their sensitivity to PARP inhibition and could provide a safe and effective combination strategy to selectively target TET deficiency in cancer.