Risk assessment in acute myeloid leukemia

Epigenetic aberrations play a central role in the pathophysiology of acute myeloid leukemia (AML). Recently, it has been demonstrated that DNA-methylation (DNAm) at a single CpG site in the gene of complement component 1 subcomponent R (C1R) is indicative for overall survival in AML. Cygenia provides analysis of the DNA-methylation level at C1R for physicians and scientists to gain better insight into disease development. 


Identification of the relevant genomic region

The genomic location with high prognostic relevance was first identified in a dataset of 194 patients from The Cancer Genome Atlas (TCGA): patients with higher methylation at this CpG site (>27% DNAm level) reveal significantly longer overall survival (53 months versus 11 months).

DNA-methylation at C1R has prognostic relevance in AML. (A) Beta-value distribution at the CpG site cg08799922 (C1R) in 656 healthy controls and 194 AML samples. (B) Kaplan-Meier curves provide estimation of overall survival (OS) in patients that were classified by median DNAm level at the relevant CpG site (C1R).


This finding was also validated in an independent set of 62 DNA-methylation profiles of cytogenetically normal AML patients (P= 0.009), and with a region-specific pyrosequencing assay in 84 AML samples (P= 0.012). Furthermore, DNA-methylation in C1R is associated with occurrence of specific genomic mutations in AML. There is evidence that DNAm at C1R is an independent prognostic marker from cytogenetic and molecular risk scores. It may be indicative for treatment response, particularly to drugs acting directly on DNA-methylation – but this needs to be addressed in further studies. Taken together, analysis of DNAm at C1R provides a simple and cost-effective biomarker for risk assessment in AML.


Relevant literature

Bozic T*, Lin Q*, et al. DNA-Methylation in C1R is a Prognostic Biomarker for Acute Myeloid Leukem. Clinical Epigenetics. 2015; 7:116.

Patent application: 2015; EP1519142.5