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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....
Language English Country Germany
Document type Journal Article, Research Support, Non-U.S. Gov't
NLK
BioMedCentral
from 2010-09-01
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Directory of Open Access Journals
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Free Medical Journals
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PubMed Central
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from 2015-01-01
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- MeSH
- Leukemia, Lymphocytic, Chronic, B-Cell drug therapy genetics MeSH
- Cyclophosphamide pharmacology therapeutic use MeSH
- Adult MeSH
- Epigenesis, Genetic drug effects MeSH
- Gene Regulatory Networks drug effects MeSH
- Immunotherapy MeSH
- Middle Aged MeSH
- Humans MeSH
- Longitudinal Studies MeSH
- DNA Methylation drug effects MeSH
- Disease Progression MeSH
- Rituximab pharmacology therapeutic use MeSH
- Oligonucleotide Array Sequence Analysis MeSH
- Aged MeSH
- Vidarabine analogs & derivatives pharmacology therapeutic use MeSH
- Treatment Outcome MeSH
- High-Throughput Nucleotide Sequencing methods MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
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 Molecular Medicine and Surgery Karolinska Institutet Stockholm Sweden
Hematology Department and HCT Unit G Papanicolaou Hospital Thessaloniki Greece
Institut d'Investigacions Biomèdiques August Pi i Sunyer Barcelona Spain
References provided by Crossref.org
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- $a Tsagiopoulou, Maria $u 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.
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- $a 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.
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