Publication details

DNA methylation profiles in chronic lymphocytic leukemia patients treated with chemoimmunotherapy

Authors

TSAGIOPOULOU M. PAPAKONSTANTINOU N. MOYSIADIS T. MANSOURI L. LJUNGSTROM V. DURAN-FERRER M. MALOUSI A. QUEIROS A.C. PLEVOVÁ Karla BHOI S. KOLLIA P. OSCIER D. ANAGNOSTOPOULOS A. TRENTIN L. RITGEN M. POSPÍŠILOVÁ Šárka STAVROYIANNI N. GHIA P. MARTIN-SUBERO J.I. POTT C. ROSENQUIST R. STAMATOPOULOS K.

Year of publication 2019
Type Article in Periodical
Magazine / Source CLINICAL EPIGENETICS
MU Faculty or unit

Central European Institute of Technology

Citation
Web https://clinicalepigeneticsjournal.biomedcentral.com/track/pdf/10.1186/s13148-019-0783-1
Doi http://dx.doi.org/10.1186/s13148-019-0783-1
Keywords DNA methylation; Chemoimmunotherapy; CLL; Microarray analysis; Relapse
Description 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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