Jak2 mediated phosphorylation and activation of TET2 in hematopoiesis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA478948 | ENA |
REPOSITORIES: ENA
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Project description:Chronic myelomonocytic leukemia (CMML) has recently been associated with a high incidence of diverse mutations in genes implicated in epigenetic mechanisms such as TET2 or EZH2. We have performed genome-wide 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 enrichment in a gene network centered in PLC, JNK and ERK, a recently described pathway involved in CMML was found, suggesting the potential role of epigenetics in the regulation of these pathways. Mutations of TET2, JAK2 and EZH2 were found in 15 patients (65.2%), 4 patients (16.6%) and 1 patient (4.1%) 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 the presence of altered karyotypes a known prognostic factor in CMML. 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. 24 samples of CMML patients, 4 healthy donor Peripheral Blood samples and 4 healthy donor Bone Marror samples
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