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DNA methylation profiles in chronic lymphocytic leukemia patients treated with chemoimmunotherapy
Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermi Rd, Thessaloniki 57001, GR, Greece;Univ Athens, Dept Biol, Athens, Greece.
Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermi Rd, Thessaloniki 57001, GR, Greece.
Ctr Res & Technol Hellas, Inst Appl Biosci, 6th Km Charilaou Thermi Rd, Thessaloniki 57001, GR, Greece;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
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2019 (English)In: Clinical Epigenetics, E-ISSN 1868-7083, Vol. 11, article id 177Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
BMC , 2019. Vol. 11, article id 177
Keywords [en]
DNA methylation, Chemoimmunotherapy, CLL, Microarray analysis, Relapse
National Category
Hematology
Identifiers
URN: urn:nbn:se:uu:diva-400829DOI: 10.1186/s13148-019-0783-1ISI: 000501362500005PubMedID: 31791414OAI: oai:DiVA.org:uu-400829DiVA, id: diva2:1384921
Funder
EU, Horizon 2020Swedish Cancer SocietySwedish Research CouncilKnut and Alice Wallenberg FoundationAvailable from: 2020-01-13 Created: 2020-01-13 Last updated: 2020-01-13Bibliographically approved

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Mansouri, LarryLjungström, ViktorBhoi, Sujata

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