DNA Methyltransferase-1 (DNMT1): A Flow Cytometric Pharmacodynamic Assay for Azacitidine Hypomethylating Therapy after Allogeneic Hematopoietic Stem Cell Transplantation (AlloSCT)

Abstract

Disease relapse is a major cause of treatment failure following alloSCT for acute myeloid leukemia (AML). Azacitidine has shown efficacy in treating, and preventing, post-transplant relapse in patients with AML. Post-SCT azacitidine administration is challenging due to the possibility of myelosuppression and an incomplete understanding of the optimal dose and schedule. DNMT1 is responsible for genome methylation in S phase and degraded after bonding irreversibly to substituted DNA. Hence, the DNMT1 level may be an attractive pharmacodynamic (PD) endpoint for azacitidine therapy