DNA methylation profiles in chronic lymphocytic leukemia patients treated with chemoimmunotherapy

Maria Tsagiopoulou, Nikos Papakonstantinou, Theodoros Moysiadis, Larry Mansouri, Viktor Ljungström, Martí Duran-Ferrer, Andigoni Malousi, Ana C. Queirós, Karla Plevova, Sujata Bhoi, Panagoula Kollia, David Oscier, Achilles Anagnostopoulos, Livio Trentin, Matthias Ritgen, Sarka Pospisilova, Niki Stavroyianni, Paolo Ghia, Jose I. Martin-Subero, Christiane PottRichard Rosenquist, Kostas Stamatopoulos

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number177
JournalClinical Epigenetics
Volume11
Issue number1
DOIs
Publication statusPublished - Dec 2 2019

Keywords

  • Chemoimmunotherapy
  • CLL
  • DNA methylation
  • Microarray analysis
  • Relapse

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Developmental Biology
  • Genetics(clinical)

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  • Cite this

    Tsagiopoulou, M., Papakonstantinou, N., Moysiadis, T., Mansouri, L., Ljungström, V., Duran-Ferrer, M., Malousi, A., Queirós, A. C., Plevova, K., Bhoi, S., Kollia, P., Oscier, D., Anagnostopoulos, A., Trentin, L., Ritgen, M., Pospisilova, S., Stavroyianni, N., Ghia, P., Martin-Subero, J. I., ... Stamatopoulos, K. (2019). DNA methylation profiles in chronic lymphocytic leukemia patients treated with chemoimmunotherapy. Clinical Epigenetics, 11(1), [177]. https://doi.org/10.1186/s13148-019-0783-1