O6-Methylguanine-DNA Methyltransferase (MGMT) Promoter Methylation and resistance of Hodgkin's Lymphoma Cells against Dacarbazine

Question: For treatment of Hodgkin's lymphoma, dacarbazine represents an effective chemotherapeutic agent. It is a prodrug that is activated in vivo to an active compound that acts mainly by generation of O6-methylguanine. This methylation can be repaired by the enzyme O6-methylguanine-DNA methyltransferase (MGMT) which transfers the methyl group to its active site and thereby inactivates itself. The MGMT promoter can be inactivated by methylation, resulting in loss of enzyme activity. Data from clinical trials from patients with glioblastoma demonstrated a strong correlation between methylation of the MGMT prom…