Study on Potentiation of ATRA Activity in HL-60 Cells by Targeting Methylation Enzymes | Chapter 2 | New Frontiers in Medicine and Medical Research Vol. 11
All Trans Retinoic Acid (ATRA) is a clinically established Differentiation Inducer (DI) for Acute Promyelocytic Leukemia (APL). Its efficacy in treating other kinds of Acute Myelocytic Leukemia (AML) is limited. ATRA targets the PML-RARA (promyelocytic leukemia/retinoic acid receptor-alpha)/DNA methyltransferase (DNMT)/Histone Deacetylase (HDAC) complex in APL, causing gene silencing to be lost and Terminal Differentiation to occur (TD). ATRA targeting of WT RARA as a single drug fails to modify the epigenetic modifications that prevent differentiation in other kinds of AML. When paired with DNMT inhibitors like 5-azacytidine, however, ATRA has better in vitro and clinical effectiveness against AML. The methylation enzyme complex (MMS), which includes Methionine Adenosyltransferase (MAT), Methyltransferase (MT), and S-Adenosylhomocysteine Hydrolase (SAHH), was previously shown to trigger differentiation in the AML M2 HL-60 cell line model. Differentiation Helper Inducers are inhibitors...