Accession Number : ADA541308


Title :   DNA Methylation as an Epigenetic Factor in the Development and Progression of Polycythemia Vera


Descriptive Note : Final rept. 15 Sep 2005-14 May 2009


Corporate Author : M D ANDERSON CANCER CENTER HOUSTON TX


Personal Author(s) : Issa, Jean-Pierre


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a541308.pdf


Report Date : Jun 2009


Pagination or Media Count : 65


Abstract : Clonal myeloproliferative disorders (MPD) affect erythroid, myelomonocytic, and megakaryocytic lineages. An activating somatic mutation of JAK2 tyrosine kinase is present in the majority of polycythemia vera (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 MPDs. We cloned 19 unique CpG islands in promoter/exon-1 regions of 15 known genes, and 4 predicted genes and annotated mRNAs as hypermethylated in PV. Using a genome-wide microarray approach, we showed distinct methylation signatures affecting hundreds of genes in MPD. We confirmed increased methylation of progesterone receptor, cadherin precursor (CDH13) and several HOX genes in MPD patients. We showed that a functional block of progesterone receptor in normal erythroid cells increased their sensitivity to erythropoietin. We demonstrated molecular responses clearing both genetic and epigenetic abnormalities after DNA-demethylation therapy in MPD patients.


Descriptors :   *DEOXYRIBONUCLEIC ACIDS , GENES , RESPONSE(BIOLOGY) , ERYTHROCYTES , ERYTHROPOIETINS , SENSE ORGANS , BLOOD DISEASES , GROWTH(PHYSIOLOGY) , METHYLATION , PROGESTERONE , DISEASES , CELLS(BIOLOGY)


Subject Categories : Biochemistry
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE