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Aging of preleukemic thymocytes drives CpG island hypermethylation in T-cell acute lymphoblastic leukemia

Cancer 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 Polycomb Repressor Complex 2 (PRC2) target genes that are not expressed in normal or malignant T-cells and which display a reciprocal association with H3K27me3 binding.

Citation:
Roels J, Thenoz M, Szarzynska B, Landfors M, De Coninck S, Demoen L, Cheung LC, Kotecha RS, et al. Aging of preleukemic thymocytes drives CpG island hypermethylation in T-cell acute lymphoblastic leukemia. Blood Cancer Discov. 2020;1(3):274-89.

Keywords:
DNA methylation; Decitabine; T-all; aging; self-renewing thymocytes

Abstract:
Cancer 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 Polycomb Repressor Complex 2 (PRC2) target genes that are not expressed in normal or malignant T-cells and which display a reciprocal association with H3K27me3 binding.