Cohesin RAD21 Gene Promoter Methylation in Patients with Acute Myeloid Leukemia

Aberrant gene promoter methylation is one of the hallmarks of Acute Myeloid Leukemia (AML). RAD21 is an important gene, implicated in sister chromatids cohesion, DNA repair, the regulation of gene transcription, apoptosis and hematopoiesis.

In this study, we investigate the possible implication of RAD21 promoter methylation in AML pathogenesis using a cohort of AML patients and a cohort of healthy individuals.

RAD21 promoter methylation was found in 24% of patients and in none of the controls (p = 0.023), indicating a possible contribution to AML development. Interestingly, a statistically higher frequency of RAD21 methylation was observed in patients with trisomy 8 (9/21, 42.9%, p = 0.021), while none of the patients with aberrations of chromosome 11 had RAD21 gene promoter methylation (0%, 0/11, p = 0.048). Patients with monosomal and complex karyotypes showed low frequencies of RAD21 methylation (7.7% and 15.4%, respectively) without reaching statistical significance. Moreover, ASXL1 mutations were not found to be associated with RAD21 methylation.

This is the first study which provides evidence for a possible pathogenetic role of RAD21 promoter methylation in AML development and especially in AML with trisomy 8. Further studies of RAD21 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.