Chronic myelomonocytic leukemia (CMML) has recently been associated with a high 
incidence of diverse mutations in genes such as TET2 or EZH2 that are implicated 
in epigenetic mechanisms. We have performed genome-wide DNA methylation arrays 
and mutational analysis of TET2, IDH1, IDH2, EZH2 and JAK2 in a group of 24 
patients with CMML. 249 genes were differentially methylated between CMML 
patients and controls. Using Ingenuity pathway analysis, we identified 
enrichment in a gene network centered around PLC, JNK and ERK suggesting that 
these pathways, whose deregulation has been recently described in CMML, are 
affected by epigenetic mechanisms. Mutations of TET2, JAK2 and EZH2 were found 
in 15 patients (65%), 4 patients (17%) and 1 patient (4%) respectively while no 
mutations in the IDH1 and IDH2 genes were identified. Interestingly, patients 
with wild type TET2 clustered separately from patients with TET2 mutations, 
showed a higher degree of hypermethylation and were associated with higher risk 
karyotypes. Our results demonstrate the presence of aberrant DNA methylation in 
CMML and identifies TET2 mutant CMML as a biologically distinct disease subtype 
with a different epigenetic profile.