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dc.contributor.authorRoels, Juliette
dc.contributor.authorThénoz, Morgan
dc.contributor.authorSzarzyńska, Bronisława
dc.contributor.authorLandfors, Mattias
dc.contributor.authorDe Coninck, Stien
dc.contributor.authorDemoen, Lisa
dc.contributor.authorProvez, Lien
dc.contributor.authorKuchmiy, Anna
dc.contributor.authorStrubbe, Steven
dc.contributor.authorReunes, Lindy
dc.contributor.authorPieters, Tim
dc.contributor.authorMatthijssens, Filip
dc.contributor.authorVan Loocke, Wouter
dc.contributor.authorErarslan-Uysal, Büşra
dc.contributor.authorRichter-Pechańska, Paulina
dc.contributor.authorDeclerck, Ken
dc.contributor.authorLammens, Tim
dc.contributor.authorDe Moerloose, Barbara
dc.contributor.authorDeforce, Dieter
dc.contributor.authorVan Nieuwerburgh, Filip
dc.contributor.authorCheung, Laurence
dc.contributor.authorKotecha, Rishi S
dc.contributor.authorMansour, Marc R
dc.contributor.authorGhesquière, Bart
dc.contributor.authorVan Camp, Guy
dc.contributor.authorBerghe, Wim Vanden
dc.contributor.authorKowalczyk, Jerzy R
dc.contributor.authorSzczepański, Tomasz
dc.contributor.authorDavé, Utpal P
dc.contributor.authorKulozik, Andreas E
dc.contributor.authorGoossens, Steven
dc.contributor.authorCurtis, David J
dc.contributor.authorTaghon, Tom
dc.contributor.authorDawidowska, Małgorzata
dc.contributor.authorDegerman, Sofie
dc.contributor.authorVan Vlierberghe, Pieter
dc.identifier.citationRoels, J. and Thénoz, M. and Szarzyńska, B. and Landfors, M. and De Coninck, S. and Demoen, L. and Provez, L. et al. 2020. Aging of preleukemic thymocytes drives CpG island hypermethylation in T-cell acute lymphoblastic leukemia. Blood Cancer Discovery. 1 (3): pp. 274-289.

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. In addition, we revealed that this aberrant methylation profile reflects the epigenetic history of T-ALL and is established already in pre-leukemic, self-renewing thymocytes that precede T-ALL development. Finally, we unexpectedly uncover that this age-related CpG island hypermethylation signature in T-ALL is completely resistant to the FDA-approved hypomethylating agent Decitabine. Altogether, we here provide conceptual evidence for the involvement of a pre-leukemic phase characterized by self-renewing thymocytes in the pathogenesis of human T-ALL.

dc.subjectDNA methylation
dc.subjectself-renewing thymocytes
dc.titleAging of preleukemic thymocytes drives CpG island hypermethylation in T-cell acute lymphoblastic leukemia.
dc.typeJournal Article
dcterms.source.titleBlood Cancer Discovery
curtin.departmentSchool of Pharmacy and Biomedical Sciences
curtin.accessStatusOpen access
curtin.facultyFaculty of Health Sciences
curtin.contributor.orcidCheung, Laurence [0000-0001-6298-5288]
curtin.contributor.orcidKotecha, Rishi S [0000-0003-1836-4075]
curtin.contributor.scopusauthoridCheung, Laurence [56663936300]

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