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Genome-wide profili...
Genome-wide profiling of histone H3 lysine 27 and lysine 4 trimethylation in multiple myeloma reveals the importance of Polycomb gene targeting and highlights EZH2 as a potential therapeutic target.
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- Agarwal, Prasoon (author)
- Uppsala universitet,Experimentell och klinisk onkologi
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- Alzrigat, Mohammad (author)
- Uppsala universitet,Experimentell och klinisk onkologi
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- Párraga, Alba Atienza (author)
- Uppsala universitet,Experimentell och klinisk onkologi
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- Enroth, Stefan (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Gyllensten
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Singh, Umashankar (author)
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- Ungerstedt, Johanna (author)
- Karolinska Institutet
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- Österborg, Anders (author)
- Karolinska Institutet
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Brown, Peter J (author)
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Ma, Anqi (author)
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Jin, Jian (author)
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- Nilsson, Kenneth (author)
- Uppsala universitet,Infektionssjukdomar
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- Öberg, Fredrik (author)
- Uppsala universitet,Experimentell och klinisk onkologi
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- Kalushkova, Antonia (author)
- Uppsala universitet,Experimentell och klinisk onkologi
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- Jernberg-Wiklund, Helena (author)
- Uppsala universitet,Experimentell och klinisk onkologi
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(creator_code:org_t)
- 2016-01-07
- 2016
- English.
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:6, s. 6809-6923
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http://www.oncotarge...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- Multiple myeloma (MM) is a malignancy of the antibody-producing plasma cells. MM is a highly heterogeneous disease, which has hampered the identification of a common underlying mechanism for disease establishment as well as the development of targeted therapy. Here we present the first genome-wide profiling of histone H3 lysine 27 and lysine 4 trimethylation in MM patient samples, defining a common set of active H3K4me3-enriched genes and silent genes marked by H3K27me3 (H3K27me3 alone or bivalent) unique to primary MM cells, when compared to normal bone marrow plasma cells. Using this epigenome profile, we found increased silencing of H3K27me3 targets in MM patients at advanced stages of the disease, and the expression pattern of H3K27me3-marked genes correlated with poor patient survival. We also demonstrated that pharmacological inhibition of EZH2 had anti-myeloma effects in both MM cell lines and CD138+ MM patient cells. In addition, EZH2 inhibition decreased the global H3K27 methylation and induced apoptosis. Taken together, these data suggest an important role for the Polycomb repressive complex 2 (PRC2) in MM, and highlights the PRC2 component EZH2 as a potential therapeutic target in MM.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- multiple myeloma; Polycomb; EZH2; H3K27me3; UNC1999
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Agarwal, Prasoon
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Alzrigat, Mohamm ...
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Párraga, Alba At ...
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Enroth, Stefan
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Singh, Umashanka ...
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Ungerstedt, Joha ...
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show more...
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Österborg, Ander ...
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Brown, Peter J
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Ma, Anqi
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Jin, Jian
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Nilsson, Kenneth
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Öberg, Fredrik
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Kalushkova, Anto ...
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Jernberg-Wiklund ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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Oncotarget
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Uppsala University
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Karolinska Institutet