Evolving DNA methylation and gene expression markers of B-cell chronic lymphocytic leukemia are present in pre-diagnostic blood samples more than 10 years prior to diagnosis

Panagiotis Georgiadis, Irene Liampa, Dennie G. Hebels, Julian Krauskopf, Aristotelis Chatziioannou, Ioannis Valavanis, Theo M. C. M. de Kok, Jos C. S. Kleinjans, Ingvar A. Bergdahl, Beatrice Melin, Florentin Spaeth, Domenico Palli, R. C. H. Vermeulen, J. Vlaanderen, Marc Chadeau-Hyam, Paolo Vineis, Soterios A. Kyrtopoulos*, EnviroGenomarkers Consortium

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

9 Citations (Web of Science)

Abstract

Background: B-cell chronic lymphocytic leukemia (CLL) is a common type of adult leukemia. It often follows an indolent course and is preceded by monoclonal B-cell lymphocytosis, an asymptomatic condition, however it is not known what causes subjects with this condition to progress to CLL. Hence the discovery of prediagnostic markers has the potential to improve the identification of subjects likely to develop CLL and may also provide insights into the pathogenesis of the disease of potential clinical relevance.

Results: We employed peripheral blood buffy coats of 347 apparently healthy subjects, of whom 28 were diagnosed with CLL 2.0-15.7 years after enrollment, to derive for the first time genome-wide DNA methylation, as well as gene and miRNA expression, profiles associated with the risk of future disease. After adjustment for white blood cell composition, we identified 722 differentially methylated CpG sites and 15 differentially expressed genes (Bonferroni-corrected p <0.05) as well as 2 miRNAs (FDR

Conclusions: Our findings demonstrate the presence in prediagnostic blood of future CLL patients, more than 10 years before diagnosis, of CLL-like cells which evolve as preclinical disease progresses, and point to early molecular alterations with a pathogenetic potential.

Original languageEnglish
Article number728
Number of pages15
JournalBMC Genomics
Volume18
DOIs
Publication statusPublished - 13 Sep 2017

Keywords

  • Epigenomics
  • Transcriptomics
  • miRNA
  • Biomarkers of risk
  • Molecular epidemiology
  • Prospective cohort
  • DISEASE PROGRESSION
  • RISK
  • CLL
  • FOXP1
  • RECEPTORS
  • LYMPHOMAS
  • DYNAMICS

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