m6A mRNA methylation control and dysregulation in AML. (A) The amount of m6A mRNA methylation in a cell is determined by the activities of methyltransferases (METTL3 and METTL14) and demethylases (eg, FTO and ALKBH5). (B) In healthy HSPCs, knockout of METLL3 reduces methylation, increases differentiation, and reduces cell growth, whereas increased METTL3 has the opposite effect. AML cells frequently have increased METTL3 and increased methylation. In AML, knockout of METTL3 leads to increased differentiation and apoptosis.