Cohesin Gene Promoter Methylation in Patients with Acute Myeloid Leukemia.

Background: Aberrant gene promoter methylation is one of the hallmarks of Acute Myeloid Leukemia (AML). is an important gene, implicated in sister chromatids cohesion, DNA repair, the regulation of gene transcription, apoptosis and hematopoiesis.

Methods: In this study, we investigate the possible implication of promoter methylation in AML pathogenesis using a cohort of AML patients and a cohort of healthy individuals.

Results: promoter methylation was found in 24% of patients and in none of the controls ( = 0.023), indicating a possible contribution to AML development. Interestingly, a statistically higher frequency of methylation was observed in patients with trisomy 8 (9/21, 42.9%, = 0.021), while none of the patients with aberrations of chromosome 11 had gene promoter methylation (0%, 0/11, = 0.048). Patients with monosomal and complex karyotypes showed low frequencies of methylation (7.7% and 15.4%, respectively) without reaching statistical significance. Moreover, mutations were not found to be associated with methylation.

Conclusions: This is the first study which provides evidence for a possible pathogenetic role of promoter methylation in AML development and especially in AML with trisomy 8. Further studies of promoter methylation in large series of different AML genetic subgroups may contribute to the elucidation of AML pathogenesis and to the identification of new epigenetic biomarkers with diagnostic and prognostic value.