p15 Hypermethylation p15 is an inhibitor of cyclin-dependent kinase-4 and a nega tive regulator of the cell cycle. Transcriptional silencing of p15 by hypermethylation commonly occurs in MDS (in contrast to inactivation of p16, which is rarely inactivated in MDS). Hypermethylation of p15 is associated with disease progression such that most MDS patients with 10% or more bone marrow blasts show this phenomenon. The importance of gene inactivation by hypermethylation in MDS generally is unknown, but the whole subject has gained in importance from clinical trials of drugs such as 5-aza-2-deoxycytidine, which can reverse hypermethylation.
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