onr:"swepub:oai:DiVA.org:uu-133207"
Search: onr:"swepub:oai:DiVA.org:uu-133207" > Polycomb target gen...
- 1 of 1
- Previous record
- Next record
- To hitlist
Polycomb target genes are silenced in multiple myeloma
-
- Kalushkova, Antonia (author)
- Uppsala universitet,Institutionen för genetik och patologi
-
- Fryknäs, Mårten (author)
- Uppsala universitet,Institutionen för genetik och patologi
- Lemaire, Miguel (author)
- show more...
- Deleu, Sarah (author)
- Atadja, Peter (author)
- Vanderkerken, Karin (author)
- show less...
- (creator_code:org_t)
- 2010-07-09
- 2010
- English.
- In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:7, s. e11483-
- Journal article (peer-reviewed)
Abstract
Subject headings
Close
- Multiple myeloma (MM) is a genetically heterogeneous disease, which to date remains fatal. Finding a common mechanism for initiation and progression of MM continues to be challenging. By means of integrative genomics, we identified an underexpressed gene signature in MM patient cells compared to normal counterpart plasma cells. This profile was enriched for previously defined H3K27-tri-methylated genes, targets of the Polycomb group (PcG) proteins in human embryonic fibroblasts. Additionally, the silenced gene signature was more pronounced in ISS stage III MM compared to stage I and II. Using chromatin immunoprecipitation (ChIP) assay on purified CD138+ cells from four MM patients and on two MM cell lines, we found enrichment of H3K27me3 at genes selected from the profile. As the data implied that the Polycomb-targeted gene profile would be highly relevant for pharmacological treatment of MM, we used two compounds to chemically revert the H3K27-tri-methylation mediated gene silencing. The S-adenosylhomocysteine hydrolase inhibitor 3-Deazaneplanocin (DZNep) and the histone deacetylase inhibitor LBH589 (Panobinostat), reactivated the expression of genes repressed by H3K27me3, depleted cells from the PRC2 component EZH2 and induced apoptosis in human MM cell lines. In the immunocompetent 5T33MM in vivo model for MM, treatment with LBH589 resulted in gene upregulation, reduced tumor load and increased overall survival. Taken together, our results reveal a common gene signature in MM, mediated by gene silencing via the Polycomb repressor complex. The importance of the underexpressed gene profile in MM tumor initiation and progression should be subjected to further studies.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
Keyword
- Haematology
- Hematologi
Publication and Content Type
- ref (subject category)
- art (subject category)
- 1 of 1
- Previous record
- Next record
- To hitlist
Find more in SwePub
- By the author/editor
- Kalushkova, Anto ...
- Fryknäs, Mårten
- Lemaire, Miguel
- Fristedt, Charlo ...
- Agarwal, Prasoon
- Eriksson, Maria
- show more...
- Deleu, Sarah
- Atadja, Peter
- Österborg, Ander ...
- Nilsson, Kenneth
- Vanderkerken, Ka ...
- Öberg, Fredrik
- Jernberg-Wiklund ...
- show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
- MEDICAL AND HEAL ...
- and Clinical Medicin ...
- and Hematology
- Articles in the publication
- PLOS ONE
- By the university
- Uppsala University
- Karolinska Institutet
Search outside SwePub
- Extend your search to:
- Google Book Search
- Google Scholar
Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.
- Copyright © LIBRIS - National Library Systems
- LIBRIS.kb.se
