Epigenetic regulation of the human telomerase reverse transciptase gene: A potential therapeutic target for the treatment of leukemia (Review)

Abstract

Telomerase activation is a critical step in human carcinogenesis through the maintenance of telomeres. Telomerase activity is primarily regulated by the human telomerase reverse transcriptase gene (hTERT), thus, an improved understanding of the transcriptional control of hTERT may provide potential therapeutic targets for the treatment of leukemia and other forms of cancer. Epigenetic modulation, a significant regulatory process in cell biology, has recently been shown to be involved in the regulation of the hTERT gene. Moreover, several epigenetic modifi ers, including DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors, are now in pre- and early clinical trials of leukemia as monotherapies or in combination with other drugs, and have achieved significant clinical success. In the present review, the epigenetic mechanisms associated with telomerase activity in leukemia, and the therapeutic potential of an antitelomerase strategy that combines epigenetic modifi ers with telomerase hTR subunit small molecule inhibitors are discussed.