Accession Number : AD1049941


Title :   Epigenetic Therapy of Hematopoietic Malignancies: Novel Approaches for Tissue-Specific and Global Inhibition of EZH2 Enzymatic Activities


Descriptive Note : Technical Report,15 Jul 2014,14 Jul 2017


Corporate Author : University of North Carolina Chapel Hill Chapel Hill United States


Personal Author(s) : Wang, Gang


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1049941.pdf


Report Date : 01 Oct 2017


Pagination or Media Count : 125


Abstract : Direct sequencing of hematopoietic cancers identified gain-of-function mutations of EZH2, the gene encoding the enzymatic subunit of Polycomb Repressive Complex-2 (PRC2), among 10% germ-center B-cell lymphomas. EZH2 silences gene expression through catalysis of methylation of histone H3 lysine 27. However, the currently available EZH2-specific inhibitors are ineffective for treating EZH2-wildtype lymphomas. Novel therapeutics needs to be developed. We found overexpression of PHF19, a PRC2-associated cofactor, is common among B-cell derived malignancies. During this funding period, we have made significant progress in testing our central hypothesis is that, overexpression of PHF19 confers oncogenicity to lymphoma by either enhancing enzymatic activities or chromatin association of PRC2 complexes; in addition, we have evaluated the pan PRC2 inhibitor as a novel means for blockade of unwanted PRC2 hyperactivities among blood cancers including B-cell malignancies.


Descriptors :   inhibitors , methylation , epigenetics , Lymphomas , enzymes , gene expression , mutations , enzyme inhibitors


Subject Categories : Medicine and Medical Research
      Genetic Engineering and Molecular Biology
      Biochemistry


Distribution Statement : APPROVED FOR PUBLIC RELEASE