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The histone methylt...
The histone methyltransferase EZH2 as a novel prosurvival factor in clinically aggressive chronic lymphocytic leukemia
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- Papakonstantinou, Nikos (författare)
- Uppsala universitet,Experimentell och klinisk onkologi,Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.
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- Ntoufa, Stavroula (författare)
- Uppsala universitet,Experimentell och klinisk onkologi,Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.
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- Chartomatsidou, Elisavet (författare)
- Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.
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- Kotta, Konstantia (författare)
- Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.
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- Agathangelidis, Andreas (författare)
- IRCCS San Raffaele Sci Inst, Div Expt Oncol, Milan, Italy.;IRCCS San Raffaele Sci Inst, Dept Oncohematol, Milan, Italy.;Univ Vita Salute San Raffaele, Milan, Italy.
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- Giassafaki, Lefki (författare)
- Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.
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- Karamanli, Tzeni (författare)
- Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.
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- Bele, Panagiota (författare)
- Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.
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- Moysiadis, Theodoros (författare)
- Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.
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- Baliakas, Panagiotis (författare)
- Uppsala universitet,Experimentell och klinisk onkologi
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- Sutton, Lesley Ann (författare)
- Uppsala universitet,Experimentell och klinisk onkologi
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- Stavroyianni, Niki (författare)
- G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece.
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- Anagnostopoulos, Achilles (författare)
- G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece.
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- Makris, Antonios M. (författare)
- Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.
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- Ghia, Paolo (författare)
- IRCCS San Raffaele Sci Inst, Div Expt Oncol, Milan, Italy.;IRCCS San Raffaele Sci Inst, Dept Oncohematol, Milan, Italy.;Univ Vita Salute San Raffaele, Milan, Italy.
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- Rosenquist, Richard (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Experimentell och klinisk onkologi
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- Stamatopoulos, Kostas (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi,Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.;G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece.
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(creator_code:org_t)
- 2016-05-14
- 2016
- Engelska.
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:24, s. 35946-35959
- Relaterad länk:
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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
Ämnesord
Stäng
- The histone methyltransferase EZH2 induces gene repression through trimethylation of histone H3 at lysine 27 (H3K27me3). EZH2 overexpression has been reported in many types of cancer and associated with poor prognosis. Here we investigated the expression and functionality of EZH2 in chronic lymphocytic leukemia (CLL). Aggressive cases with unmutated IGHV genes (U-CLL) displayed significantly higher EZH2 expression compared to indolent CLL cases with mutated IGHV genes (M-CLL); furthermore, in U-CLL EZH2 expression was upregulated with disease progression. Within U-CLL, EZH2(high) cases harbored significantly fewer (p = 0.033) TP53 gene abnormalities compared to EZH2(low) cases. EZH2(high) cases displayed high H3K27me3 levels and increased viability suggesting that EZH2 is functional and likely confers a survival advantage to CLL cells. This argument was further supported by siRNA-mediated downmodulation of EZH2 which resulted in increased apoptosis. Notably, at the intraclonal level, cell proliferation was significantly associated with EZH2 expression. Treatment of primary CLL cells with EZH2 inhibitors induced downregulation of H3K27me3 levels leading to increased cell apoptosis. In conclusion, EZH2 is overexpressed in adverse-prognosis CLL and associated with increased cell survival and proliferation. Pharmacologic inhibition of EZH2 catalytic activity promotes apoptosis, highlighting EZH2 as a novel potential therapeutic target for specific subgroups of patients with CLL.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- CLL
- EZH2
- apoptosis
- proliferation
- inhibitors
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Papakonstantinou ...
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Ntoufa, Stavroul ...
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Chartomatsidou, ...
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Kotta, Konstanti ...
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Agathangelidis, ...
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Giassafaki, Lefk ...
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Karamanli, Tzeni
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Bele, Panagiota
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Moysiadis, Theod ...
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Baliakas, Panagi ...
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Sutton, Lesley A ...
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Stavroyianni, Ni ...
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Anagnostopoulos, ...
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Makris, Antonios ...
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Ghia, Paolo
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Rosenquist, Rich ...
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Stamatopoulos, K ...
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Uppsala universitet