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.

• 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