DNA Methylation as an Epigenetic Factor in the Development and Progression of Polycythemia Vera
Abstract
Polycythemia vera (PV) is a clonal myeloproliferative disorder (MPD) affecting erythroid, myelomonocytic, and megakaryocytic lineages. An activating somatic mutation of JAK2 tyrosine kinase is present in the majority of PV patients but also in 50% of patients with essential thrombocythemia (ET) and myelofibrosis (MF). Additonal factors are presumed to affect the phenotype and progression of the disease. We studied DNA methylation as a possible epigenetic factor in the development and progression of polycythemia vera and related MPDs. We cloned 19 unique CpG islands in promoter/exon-1 regions of 15 known genes, and 4 predicted genes and annotated mRNAs as potentially hypermethylated in PV. We confirmed increased methylation of progesterone receptor and cadherin precursor (CDH13) in a subset of PV, MF and AML patients. We showed that a functional block of progesterone receptor in normal erythroid cells increases their sensitivity to erythropoietin. Silencing of these genes by methylation may contribute to disease development by altering the response of hematopoietic cells to proliferative stimuli or their interactions with stroma.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2006
- Accession Number
- ADA463306
Entities
People
- Jaroslav Jelinek
- Jean-pierre Issa
Organizations
- The University of Texas MD Anderson Cancer Center