GSE155332 Aging of preleukemic thymocytes drives CpG island hypermethylation in T-cell acute lymphoblastic leukemia [ChIPmentation_TALL]

Contributors : Juliette Roels ; Morgan Th énoz ; Pieter Van VlierbergheSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensCancer cells display DNA hypermethylation at specific CpG islands in comparison to their normal healthy counterparts, but the mechanism that drives this so-called CpG island methylator phenotype (CIMP) remains poorly understood. Here, we show that CpG island methylation in human T-cell acute lymphoblastic leukemia (T-ALL) mainly occurs at promoters of PRC2 target genes that are not expressed in normal or malignant T-cells and which display a reciprocal association with H3K27me3 binding. In addition, we found that this aberrant methylation profile shows a strong correlation with the epigenetic age of the leukemic T cells and elucidate that a similar CpG island methylation signature is gradually established in aging pre-leukemic thymocytes from CD2-Lmo2 transgenic mice. Finally, we unexpectedly uncover that this age-related CpG island hypermethylation signature is completely resistant to the FDA-approved hypomethylating agent Decitabine. Altogether, our work demonstrates that DNA methylation reflects the epigenetic history of leukemic T cells and suggests that methylation-based subtypes of human T-ALL have followed a different trajectory towards T-cell transformation, possibly mediated by differences in the self-renewing capacity of the putative T-ALL cell-of-origin. Given that the concept of preleukemic ...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Homo sapiens Source Type: research