The notion that gene silencing after methylation of promoters of tumor suppresser genes results in carcinogenesis is supported by many lines of evidence. Myelodysplastic syndrome (MDS) is a stem cell disorder that is characterized by frequent evolution to acute myelogenous leukemia. We found that aberrant methylation of the promoter region of the p15INK4B gene is frequent in MDS, that this plays an important role in clonal expansion in MDS and that it might be related to disease progression. 1 We also reported that the p15INK4B gene is methylated not only in the blast population, but also in differentiated cells among MDS patients, suggesting that p15INK4B methylation is an early event in MDS. 2, 3 However, the molecular mechanism (s) responsible for aberrant methylation of the p15INK4B gene in MDS remains obscure.

DNA methyltransferases (DNMT) are the enzymes responsible for DNA methylation and DNMTs 1, 3a and 3b have been identified in vivo. Levels of DNMT1 activities are high in many cultured tumor cell lines. 4 However, the results of studies analyzing the expression levels or total DNA methyltransferase activity in human cancers are contradictory. 5–8 Among hematological