Increased activity of histone deacetylases in childhood acute lymphoblastic leukaemia and acute myeloid leukaemia: Support for histone deacetylase inhibitors as antileukaemic agents

摘要

The importance of epigenetic mechanisms, such as DNA methylation and histone acetylation, in human cancer development is becoming increasingly clear (Bolden et al, 2006; Chen et al, 2010). Genomic analyses of patient samples have revealed that genes encoding chromatin modifier proteins are among the most frequently mutated genes in cancer (Morin et al, 2011; Mullighan et al, 2011; Pasqualucci et al, 2011). In particular, a reduced level of histone acetylation is widespread among cancers (Fraga et al, 2005). Consequently, drugs that enhance histone acetylation, termed histone deacetylase inhibitors (HDACi) (Bolden et al, 2006), have been clinically tested, and two of them, vorinostat and romidepsin, have received approval by the US Food and Drug Administration as second-line treatments for cutaneous T cell lymphoma.