Through the looking glass

DNA methylation is a common mode of gene silencing in cancer, and MDS remains the poster child for a disease in which targeting the DNMT enzymes leads to clinical benefit.^1-4 However, some important questions remain unanswered, 2 of which are directly addressed in this issue of Blood by Figueroa and colleagues⁵: What pivotal gene sets are silenced by DNA methylation in MDS and de novo AML, a question that begs a reference to the patterns of normal marrow cells on a genome-wide scale, and what global changes in DNA methylation can be achieved when treating patients with DNMT inhibitors?