Clinical epigenetics · 2019
DNA methylation profiles in chronic lymphocytic leukemia patients treated with chemoimmunotherapy.
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Tsagiopoulou Maria, Papakonstantinou Nikos, Moysiadis Theodoros, Mansouri Larry, Ljungström Viktor, Duran-Ferrer Martí, Malousi Andigoni, Queirós Ana C, Plevova Karla, Bhoi Sujata, Kollia Panagoula, Oscier David, Anagnostopoulos Achilles, Trentin Livio, Ritgen Matthias, Pospisilova Sarka, Stavroyianni Niki, Ghia Paolo, Martin-Subero Jose I, Pott Christiane, Rosenquist Richard, Stamatopoulos Kostas
Аннотация
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.
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.
Предметные рубрики MeSH
AdultAgedCyclophosphamideDNA MethylationDisease ProgressionEpigenesis, GeneticFemaleGene Regulatory NetworksHigh-Throughput Nucleotide SequencingHumansImmunotherapyLeukemia, Lymphocytic, Chronic, B-CellLongitudinal StudiesMaleMiddle AgedOligonucleotide Array Sequence AnalysisRituximabTreatment OutcomeVidarabine