TY - JOUR
TI - DNA methylation profiles in chronic lymphocytic leukemia patients treated with chemoimmunotherapy
AU - Tsagiopoulou, M.
AU - Papakonstantinou, N.
AU - Moysiadis, T.
AU - Mansouri, L.
AU - Ljungström, V.
AU - Duran-Ferrer, M.
AU - Malousi, A.
AU - Queirós, A.C.
AU - Plevova, K.
AU - Bhoi, S.
AU - Kollia, P.
AU - Oscier, D.
AU - Anagnostopoulos, A.
AU - Trentin, L.
AU - Ritgen, M.
AU - Pospisilova, S.
AU - Stavroyianni, N.
AU - Ghia, P.
AU - Martin-Subero, J.I.
AU - Pott, C.
AU - Rosenquist, R.
AU - Stamatopoulos, K.
JO - Clinical Epigenetics
PY - 2019
VL - 11
TODO - 1
SP - null
PB - BioMed Central Ltd.
SN - 1868-7075, 1868-7083
TODO - 10.1186/s13148-019-0783-1
TODO - bendamustine;  cyclophosphamide;  fludarabine;  mitoxantrone;  rituximab;  transcription factor;  cyclophosphamide;  fludarabine;  rituximab;  vidarabine, adult;  aged;  Article;  binding site;  cancer combination chemotherapy;  cancer growth;  cancer immunotherapy;  cancer patient;  chemoimmunotherapy;  chromatin;  chronic lymphatic leukemia;  clinical article;  clinical feature;  controlled study;  cytogenetics;  DNA methylation;  drug response;  epigenetic burden;  epigenetics;  female;  genomics;  human;  human cell;  immunoglobulin heavy chain gene;  leukemia relapse;  male;  memory cell;  middle aged;  oncological parameters;  priority journal;  relapse changes;  time to first treatment;  time to relapse;  chronic lymphatic leukemia;  disease exacerbation;  DNA methylation;  DNA microarray;  drug effect;  gene regulatory network;  genetic epigenesis;  genetics;  high throughput sequencing;  immunotherapy;  longitudinal study;  procedures;  treatment outcome, Adult;  Aged;  Cyclophosphamide;  Disease Progression;  DNA Methylation;  Epigenesis, Genetic;  Female;  Gene Regulatory Networks;  High-Throughput Nucleotide Sequencing;  Humans;  Immunotherapy;  Leukemia, Lymphocytic, Chronic, B-Cell;  Longitudinal Studies;  Male;  Middle Aged;  Oligonucleotide Array Sequence Analysis;  Rituximab;  Treatment Outcome;  Vidarabine
TODO - 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. © 2019 The Author(s).
ER -