DNA Methyltransferase-1 (DNMT1): A Flow Cytometric Pharmacodynamic Assay for Azacitidine Hypomethylating Therapy after Allogeneic Hematopoietic Stem Cell Transplantation (AlloSCT)
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DNA Methyltransferase-1 (DNMT1): A Flow Cytometric Pharmacodynamic Assay for Azacitidine Hypomethylating Therapy after Allogeneic Hematopoietic Stem Cell Transplantation (AlloSCT)
M William, Basem; Woost, Philip; Mahfouz, Reda; Brister, Lauren; Caimi, Paolo; Campagnaro, Erica; Cooper, Brenda; M Lazarus, Hillard; Saunthararajah, Yogen; JG de Lima, Marcos; V Komanduri, Krishna; Jacobberger, James
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
