The TET enzymes are α-ketoglutarate and Fe2+-dependent dioxygenases that catalyze oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). Loss of TET2, as commonly encountered in myeloid neoplasms and clonal hematopoiesis, results in aberrant hematopoietic stem cell self-renewal. Treatment with vitamin C, a cofactor of α-ketoglutarate and Fe2+-dependent dioxygenases, restores TET enzymatic activity and suppresses leukemia formation (vitamin C enters hematopoietic stem cells via the transporter Slc23a2). Moreover, TET2 mediated DNA oxidation induced by vitamin C enhances sensitivity to PARP inhibition.