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Integrated epigenom...
Integrated epigenomic and transcriptomic analysis reveals TP63 as a novel player in clinically aggressive chronic lymphocytic leukemia
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- Papakonstantinou, Nikos (författare)
- Uppsala University,Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab,Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermi Rd, GR-57001 Thessaloniki, Greece,Center for Research and Technology Hellas
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- Ntoufa, Stavroula (författare)
- Uppsala University,Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab,Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermi Rd, GR-57001 Thessaloniki, Greece,Center for Research and Technology Hellas
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- Tsagiopoulou, Maria (författare)
- Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermi Rd, GR-57001 Thessaloniki, Greece,Center for Research and Technology Hellas
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- Moysiadis, Theodoros (författare)
- Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermi Rd, GR-57001 Thessaloniki, Greece,Center for Research and Technology Hellas
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- Bhoi, Sujata (författare)
- Uppsala University,Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab
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- Malousi, Andigoni (författare)
- Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermi Rd, GR-57001 Thessaloniki, Greece;Aristotle Univ Thessaloniki, Med Sch, Lab Biol Chem, Thessaloniki, Greece,Aristotle University of Thessaloniki,Center for Research and Technology Hellas
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- Psomopoulos, Fotis (författare)
- Karolinska Institute,Karolinska Institutet,Center for Research and Technology Hellas
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- Mansouri, Larry (författare)
- Uppsala University,Karolinska Institute,Uppsala universitet,Science for Life Laboratory, SciLifeLab,Experimentell och klinisk onkologi,Karolinska Institutet, Dept Mol Med & Surg, Stockholm, Sweden
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- Laidou, Stamatia (författare)
- Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermi Rd, GR-57001 Thessaloniki, Greece,Center for Research and Technology Hellas
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- Papazoglou, Despoina (författare)
- Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermi Rd, GR-57001 Thessaloniki, Greece,Center for Research and Technology Hellas
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- Gounari, Maria (författare)
- Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermi Rd, GR-57001 Thessaloniki, Greece,Center for Research and Technology Hellas
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- Pasentsis, Konstantinos (författare)
- Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermi Rd, GR-57001 Thessaloniki, Greece,Center for Research and Technology Hellas
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- Plevova, Karla (författare)
- Univ Hosp Brno, Ctr Mol Biol & Gene Therapy, Dept Internal Med Hematol & Oncol, Brno, Czech Republic;Masaryk Univ, Med Fac, Brno, Czech Republic,University Hospital Brno
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- Kuci-Emruli, Venera (författare)
- Lund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH
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- Duran-Ferrer, Marti (författare)
- Univ Barcelona, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Dept Fundamentos Clin, Barcelona, Spain,University of Barcelona
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- Davis, Zadie (författare)
- Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England,Royal Bournemouth Hospital
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- Ek, Sara (författare)
- Lund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH
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- Rossi, Davide (författare)
- Oncol Inst Southern Switzerland, Hematol, Bellinzona, Switzerland;Inst Oncol Res, Bellinzona, Switzerland,Oncology Institute of Southern Switzerland
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- Gaidano, Gianluca (författare)
- Amedeo Avogadro Univ Eastern Piedmt, Dept Translat Med, Div Hematol, Novara, Italy,University of Eastern Piedmont
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- Ritgen, Matthias (författare)
- Univ Hosp Schleswig Holstein, Med Dept 2, Kiel, Germany,University Medical Center Schleswig-Holstein
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- Oscier, David (författare)
- Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England,Royal Bournemouth Hospital
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- Stavroyianni, Niki (författare)
- G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece,George Papanicolaou General Hospital
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- Pospisilova, Sarka (författare)
- Univ Hosp Brno, Ctr Mol Biol & Gene Therapy, Dept Internal Med Hematol & Oncol, Brno, Czech Republic;Masaryk Univ, Med Fac, Brno, Czech Republic,University Hospital Brno
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- Davi, Frederic (författare)
- Hematol Dept, Paris, France;Univ Paris 06, Paris, France,Paris-Sorbonne University
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- Ghia, Paolo (författare)
- IRCCS San Raffaele Sci Inst, Dept Oncohematol, Div Expt Oncol, Milan, Italy;Univ Vita Salute San Raffaele, Milan, Italy,Vita-Salute San Raffaele University
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- Hadzidimitriou, Anastasia (författare)
- Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermi Rd, GR-57001 Thessaloniki, Greece,Center for Research and Technology Hellas
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- Belessi, Chrysoula (författare)
- Nikea Gen Hosp, Hematol Dept, Athens, Greece,Nikea General Hospital, Piraeus
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- Martin-Subero, Jose, I (författare)
- Univ Barcelona, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Dept Fundamentos Clin, Barcelona, Spain,University of Barcelona
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- Pott, Christiane (författare)
- Univ Hosp Schleswig Holstein, Med Dept 2, Kiel, Germany,University Medical Center Schleswig-Holstein
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- Rosenquist, Richard (författare)
- Uppsala University,Karolinska Institute,Uppsala universitet,Science for Life Laboratory, SciLifeLab,Experimentell och klinisk onkologi,Karolinska Institutet, Dept Mol Med & Surg, Stockholm, Sweden
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- Stamatopoulos, Kostas (författare)
- Uppsala University,Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab,Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermi Rd, GR-57001 Thessaloniki, Greece,Center for Research and Technology Hellas
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(creator_code:org_t)
- 2019-01-15
- 2019
- Engelska.
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 144:11, s. 2695-2706
- Relaterad länk:
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https://onlinelibrar...
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http://dx.doi.org/10...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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https://lup.lub.lu.s...
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Abstract
Ämnesord
Stäng
- Chronic lymphocytic leukemia (CLL) stereotyped subsets #6 and #8 include cases expressing unmutated B cell receptor immunoglobulin (BcR IG) (U-CLL). Subset #6 (IGHV1-69/IGKV3-20) is less aggressive compared to subset #8 (IGHV4-39/IGKV1(D)-39) which has the highest risk for Richter's transformation among all CLL. The underlying reasons for this divergent clinical behavior are not fully elucidated. To gain insight into this issue, here we focused on epigenomic signatures and their links with gene expression, particularly investigating genome-wide DNA methylation profiles in subsets #6 and #8 as well as other U-CLL cases not expressing stereotyped BcR IG. We found that subset #8 showed a distinctive DNA methylation profile compared to all other U-CLL cases, including subset #6. Integrated analysis of DNA methylation and gene expression revealed significant correlation for several genes, particularly highlighting a relevant role for the TP63 gene which was hypomethylated and overexpressed in subset #8. This observation was validated by quantitative PCR, which also revealed TP63 mRNA overexpression in additional nonsubset U-CLL cases. BcR stimulation had distinct effects on p63 protein expression, particularly leading to induction in subset #8, accompanied by increased CLL cell survival. This pro-survival effect was also supported by siRNA-mediated downregulation of p63 expression resulting in increased apoptosis. In conclusion, we report that DNA methylation profiles may vary even among CLL patients with similar somatic hypermutation status, supporting a compartmentalized approach to dissecting CLL biology. Furthermore, we highlight p63 as a novel prosurvival factor in CLL, thus identifying another piece of the complex puzzle of clinical aggressiveness. What's new? In chronic lymphocytic leukemia (CLL), cases with unmutated immunoglobulin receptors (U-CLL) are generally associated with inferior outcome, albeit still displaying considerable heterogeneity. Might such differences in CLL progression be explained by epigenetics? In this study, the authors found that an unusually aggressive subset of CLLs called subset #8 has a distinctive DNA-methylation profile. They also found that p63 is a novel pro-survival factor for CLL cells. These molecular studies may lead to new prognostic biomarkers, and possibly new therapeutic targets, for CLL.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Nyckelord
- CLL
- stereotypy
- DNA methylation
- gene expression
- TP63
- CLL
- DNA methylation
- gene expression
- stereotypy
- TP63
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Papakonstantinou ...
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Ntoufa, Stavroul ...
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Tsagiopoulou, Ma ...
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Moysiadis, Theod ...
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Bhoi, Sujata
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Malousi, Andigon ...
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visa fler...
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Psomopoulos, Fot ...
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Mansouri, Larry
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Laidou, Stamatia
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Papazoglou, Desp ...
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Gounari, Maria
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Pasentsis, Konst ...
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Plevova, Karla
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Kuci-Emruli, Ven ...
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Duran-Ferrer, Ma ...
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Davis, Zadie
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Ek, Sara
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Rossi, Davide
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Gaidano, Gianluc ...
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Ritgen, Matthias
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Oscier, David
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Stavroyianni, Ni ...
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Pospisilova, Sar ...
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Davi, Frederic
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Ghia, Paolo
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Hadzidimitriou, ...
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Belessi, Chrysou ...
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Martin-Subero, J ...
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Pott, Christiane
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Rosenquist, Rich ...
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Stamatopoulos, K ...
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