Related Experiment Video
Updated: May 17, 2026
Comprehensive DNA Methylation Analysis Using a Methyl-CpG-binding Domain Capture-based Method in Chronic Lymphocytic Leukemia Patients
Published on: June 16, 2017
Methylome profiling reveals distinct alterations in phenotypic and mutational subgroups of myeloproliferative
Sangeeta Nischal1, Sanchari Bhattacharyya, Maximilian Christopeit
1Albert Einstein College of Medicine, Bronx, New York; Mayo Clinic, Rochester, MN, USA.
Abstract:
Even though mutations in epigenetic regulators frequently occur in myeloproliferative neoplasms, their effects on the epigenome have not been well studied. Furthermore, even though primary myelofibrosis (PMF) has a markedly worse prognosis than essential thrombocytosis or polycythemia vera, the molecular distinctions between these subgroups are not well elucidated. We conducted the HELP (HpaII tiny fragment enriched by LM-PCR) assay to study genome-wide methylation in polycythemia vera, essential thrombocytosis, and PMF samples compared with healthy controls. We determined that polycythemia vera and essential thrombocytosis are characterized by aberrant promoter hypermethylation, whereas PMF is an epigenetically distinct subgroup characterized by both aberrant hyper- and hypomethylation. Aberrant hypomethylation in PMF was seen to occur in non-CpG island loci, showing further qualitative differences between the disease subgroups. The differentially methylated genes in polycythemia vera and essential thrombocytosis were involved predominantly in cell signaling pathways and were enriched for binding sites of GATA1 and other transcription factors. In contrast, aberrantly methylated genes in PMF were involved in inflammatory pathways and were enriched for NF1, LEF1, and other transcription factors. Within the PMF subgroup, cases with ASXL1 disruptions formed an epigenetically distinct subgroup with relatively increased methylation. Cases of myeloproliferative neoplasms (MPN) with TET2 mutations showed decreased levels of hydroxymethylation and distinct set of hypermethylated genes. In contrast, the JAK2V617F mutation did not drive epigenetic clustering within MPNs. Finally, the significance of aberrant methylation was shown by sensitivity of MPN-derived cell lines to decitabine. These results show epigenetic differences between PMF and polycythemia vera/essential thrombocytosis and reveal methylomic signatures of ASXL1 and TET2 mutations.
Insights
Myeloproliferative neoplasms (MPN) show distinct epigenetic profiles. Primary myelofibrosis (PMF) is epigenetically unique, differing from polycythemia vera and essential thrombocytosis, with specific methylation patterns linked to mutations.
Area of Science:
- Genomics
- Epigenetics
- Hematology
Background:
- Mutations in epigenetic regulators are common in myeloproliferative neoplasms (MPNs).
- The epigenetic effects of these mutations and molecular distinctions between MPN subtypes (PMF, ET, PV) remain poorly understood.
- Primary myelofibrosis (PMF) has a worse prognosis than essential thrombocytosis (ET) or polycythemia vera (PV).
Purpose of the Study:
- To investigate genome-wide DNA methylation patterns in MPN subtypes.
- To identify epigenetic differences between PMF, ET, and PV.
- To correlate epigenetic alterations with specific mutations (ASXL1, TET2, JAK2V617F) and assess therapeutic implications.
Main Methods:
- Genome-wide methylation analysis using the HELP (HpaII tiny fragment enriched by LM-PCR) assay.
- Comparison of methylation profiles in samples from patients with PV, ET, PMF, and healthy controls.
- Analysis of gene methylation patterns and enrichment of transcription factor binding sites.
Main Results:
- PV and ET exhibit aberrant promoter hypermethylation.
- PMF is epigenetically distinct, showing both aberrant hyper- and hypomethylation, particularly at non-CpG island loci.
- Methylated genes in PV/ET are involved in cell signaling, while PMF genes are linked to inflammatory pathways.
- ASXL1 mutations define a distinct epigenetic subgroup within PMF with increased methylation.
- TET2 mutations are associated with decreased hydroxymethylation and a unique set of hypermethylated genes.
- JAK2V617F mutation did not drive epigenetic clustering.
- MPN cell lines demonstrated sensitivity to decitabine, indicating the functional relevance of aberrant methylation.
Conclusions:
- Epigenetic profiles differ significantly between PMF and PV/ET.
- Distinct methylomic signatures are associated with ASXL1 and TET2 mutations in MPNs.
- Aberrant DNA methylation is a potential therapeutic target in MPNs, as shown by decitabine sensitivity.
More Related Videos
Related Concept Videos
01:15Differentiation of Common Myeloid Progenitor Cells
02:23Abnormal Proliferation