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

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. Transcriptional differences between paired intraclonal fractions confirmed their proliferative experience and further supported a linear advancement from PF to RF in the peripheral blood. Marked expression differences in intraclonal fractions suggest potential pathological and therapeutic relevance of studying intraclonal CLL fractions as compared to bulk cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE144896 | GEO | 2020/03/16

REPOSITORIES: GEO

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

Project description: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.

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Homo sapiens

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2014-05-15 | GSE53236 | GEO

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