Genomics,Multiomics

Dataset Information

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CLL intraclonal fractions exhibit established and recently-acquired patterns of DNA methylation [ME]


ABSTRACT: Intraclonal subpopulations of circulating chronic lymphocytic leukemia (CLL) cells with different proliferative histories and reciprocal surface expression of CXCR4 and CD5 have been observed in the peripheral blood of CLL patients and named proliferative (PF), intermediate (IF) and resting (RF) cellular fractions. Here we found that these intraclonal circulating fractions share persistent DNA methylation signatures largely associated with the mutation status of the immunoglobulin heavy chain locus (IGHV) and their origins from distinct stages of differentiation of antigen-experienced B-cells. Increased leukemic birth rate (BR), however, showed a very limited impact on DNA methylation of circulating CLL fractions independent of IGHV mutation status. Additionally, DNA methylation heterogeneity increased as leukemic cells advanced from PF to RF in the peripheral blood. This frequently co-occurred with heterochromatin hypomethylation and hypermethylation of Polycomb-repressed regions in the PF, suggesting accumulation of longevity-associated epigenetic features in recently born cells. Overall design: Genome-wide DNA methylation profiling of sorted, fractionated peripheral blood mononuclear cell (PBMC) samples from patients with CLL. For 21 patients, enough data was obtained to study the DNA methylation using Illumina 450K beadarrays in 4 fractions, and matching RNA expression. Patients had known differences in IGHV mutational status , as well as cellular birth rates, as determined by labeling with deuterated water ingested by the patients.

INSTRUMENT(S): Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)

ORGANISM(S): Homo sapiens  

SUBMITTER: Boris Bartholdy 

PROVIDER: GSE144894 | GEO | 2020-03-16

REPOSITORIES: GEO

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Intraclonal subpopulations of circulating chronic lymphocytic leukemia (CLL) cells with different proliferative histories and reciprocal surface expression of CXCR4 and CD5 have been observed in the peripheral blood of CLL patients and named proliferative (PF), intermediate (IF), and resting (RF) cellular fractions. Here, we found that these intraclonal circulating fractions share persistent DNA methylation signatures largely associated with the mutation status of the immunoglobulin heavy chain  ...[more]

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