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DNA methylation profiles in chronic lymphocytic leukemia patients treated with chemoimmunotherapy

M. Tsagiopoulou, N. Papakonstantinou, T. Moysiadis, L. Mansouri, V. Ljungström, M. Duran-Ferrer, A. Malousi, AC. Queirós, K. Plevova, S. Bhoi, P. Kollia, D. Oscier, A. Anagnostopoulos, L. Trentin, M. Ritgen, S. Pospisilova, N. Stavroyianni, P....

. 2019 ; 11 (1) : 177. [pub] 20191202

Jazyk angličtina Země Německo

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc20025414

BACKGROUND: In order to gain insight into the contribution of DNA methylation to disease progression of chronic lymphocytic leukemia (CLL), using 450K Illumina arrays, we determined the DNA methylation profiles in paired pre-treatment/relapse samples from 34 CLL patients treated with chemoimmunotherapy, mostly (n = 31) with the fludarabine-cyclophosphamide-rituximab (FCR) regimen. RESULTS: The extent of identified changes in CLL cells versus memory B cells from healthy donors was termed "epigenetic burden" (EB) whereas the number of changes between the pre-treatment versus the relapse sample was termed "relapse changes" (RC). Significant (p < 0.05) associations were identified between (i) high EB and short time-to-first-treatment (TTFT); and, (ii) few RCs and short time-to-relapse. Both the EB and the RC clustered in specific genomic regions and chromatin states, including regulatory regions containing binding sites of transcription factors implicated in B cell and CLL biology. CONCLUSIONS: Overall, we show that DNA methylation in CLL follows different dynamics in response to chemoimmunotherapy. These epigenetic alterations were linked with specific clinical and biological features.

2nd Medical Department University Hospital Schleswig Holstein Campus Kiel Kiel Germany

Department of Biology National and Kapodistrian University of Athens Athens Greece

Department of Haematology Royal Bournemouth Hospital Bournemouth UK

Department of Immunology Genetics and Pathology Science for Life Laboratory Uppsala University Uppsala Sweden

Department of Internal Medicine Hematology and Oncology University Hospital Brno and Medical Faculty of Masaryk University Brno Czech Republic Central European Institute of Technology Masaryk University Brno Czech Republic

Department of Medicine Hematology and Clinical Immunology Branch Padua University School of Medicine Padua Italy

Department of Molecular Medicine and Surgery Karolinska Institutet Stockholm Sweden

Department of Molecular Medicine and Surgery Karolinska Institutet Stockholm Sweden Department of Immunology Genetics and Pathology Science for Life Laboratory Uppsala University Uppsala Sweden

Division of Experimental Oncology and Department of Onco Hematology IRCCS San Raffaele Scientific Institute and Università Vita Salute San Raffaele Milan Italy

Hematology Department and HCT Unit G Papanicolaou Hospital Thessaloniki Greece

Institut d'Investigacions Biomèdiques August Pi i Sunyer Barcelona Spain

Institut d'Investigacions Biomèdiques August Pi i Sunyer Departamento de Fundamentos Clínicos Universitat de Barcelona Barcelona Spain

Institute of Applied Biosciences Center for Research and Technology Hellas 6th km Charilaou Thermi Rd 57001 Thermi Thessaloniki GR Greece

Institute of Applied Biosciences Center for Research and Technology Hellas 6th km Charilaou Thermi Rd 57001 Thermi Thessaloniki GR Greece Department of Biology National and Kapodistrian University of Athens Athens Greece

Institute of Applied Biosciences Center for Research and Technology Hellas 6th km Charilaou Thermi Rd 57001 Thermi Thessaloniki GR Greece Department of Molecular Medicine and Surgery Karolinska Institutet Stockholm Sweden

Laboratory of Biological Chemistry Medical School Aristotle University of Thessaloniki Thessaloniki Greece

Citace poskytuje Crossref.org

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