Diminished expression of 5hmc in Reed-Sternberg cells in classical Hodgkin lymphoma is a common epigenetic marker

•5hmC is universally depleted in Reed-Sternberg cells.•Pharmacologic treatment with vitamin C induced apoptosis and replenished 5hmC content in a Hodgkin disease cell line.•Epigenetic therapies may be of benefit in classical Hodgkin lymphoma. Loss of the epigenetic marker 5-hydroxymethylcytosine (5hmC) has been demonstrated in a variety of neoplasms. Several recent studies have shown epigenetic alteration in Classical Hodgkin lymphoma (CHL), which may impact treatment. We demonstrate near universal depletion of 5hmC in the neoplastic Hodgkin Reed-Sternberg (H/RS) cells in all cases of CHL (49/49). We hypothesized that the addition of vitamin C–a cofactor for the ten-eleven translocation (TET) enzymes which oxidize 5-methylcytosine (5mC) to 5hmC - may replenish levels of 5hmC. The CHL cell line L428 was grown in optimal conditions and then subjected to vitamin C treatment, which demonstrated reduced cell viability as well as caspase activation and increased concentration of 5hmC. A more detailed understanding of the epigenetic landscape of CHL may help guide future therapies.