Altered methylation levels in elderly acute myeloid leukaemia patients compared to elderly well individuals

摘要

Epigenetic alterations, such as aberrant DNA methylation, can result in gene silencing, particularly of tumour suppressor genes during leukaemogenesis (Dellett et al, 2010; Fabiani et al, 2010). Hyper-methylation has been associated with silencing of genes involved in cell cycle regulation and DNA repair among other functions. Promoter hyper-methylation of the CDKN2A gene has been documented in different cancer types. While the genetic aberrations occurring in acute myeloid leukaemia (AML) are fairly well understood, the associated epigenetic deregulation remains to be determined. Moreover, increasing evidence supports a role for epigenetic lesions and perturbations in the aetiology of ageing (Gravina & Vijg, 2010) which may be partly due to the accumulation of errors in DNA methylation. Few studies have investigated methylation patterns in elderly well individuals. A study of non-cancer patients aged between 45 and 75 years showed LIRE1 (long interspersed nuclear element-1, retro-transposable element) (a proxy for global DNA methylation) methylation was stable, with some discrimination for gender and race/ethnicity (Kitkumthorn & Mutirangura, 2011; Zhang et al, 2011).