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DNA methylation profile in chronic myelomonocytic leukemia associates with distinct clinical, biological and genetic features

ABSTRACT: Chromosomal abnormalities are detected in 20-30% of patients with chronic myelomonocytic leukemia (CMML) and correlate with prognosis. Epigenetic abnormalities are frequent in CMML, including mutations in DNA methylation and histone-modifying enzymes, but the methylation profile is not well characterized in these patients. In this study we performed DNA methylation microarrays in 65 CMML patients and 10 healthy controls. Differential methylation analysis between patients and controls allowed us to identify abnormalities in DNA methylation including hypermethylated genes, large genome regions with aberrant DNA methylation and altered cellular pathways. Hierarchical cluster analysis identified two main clusters that associated with the clinical, biological and genetic features of patients. Group 1 was enriched in patients that presented with adverse clinical and biological characteristics and that had a poorer overall survival and progression free survival. In addition, significant differences in DNA methylation was observed between patients with low risk and intermediate/high risk karyotypes and between TET2 mutant and wild-type patients. These results demonstrate that DNA methylation is altered in CMML and is associated with distinct biological and clinical features. Furthermore, these results may provide a useful basis for identifying new therapeutic targets.

ORGANISM(S): Homo sapiens

PROVIDER: GSE105420 | GEO | 2017/11/17

SECONDARY ACCESSION(S): PRJNA415143

REPOSITORIES: GEO

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