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 lymphob...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2020
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| Subjects: | |
| Online Access: | http://hdl.handle.net/20.500.11937/81750 |
| _version_ | 1848764411935719424 |
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| author | Roels, Juliette Thénoz, Morgan Szarzyńska, Bronisława Landfors, Mattias De Coninck, Stien Demoen, Lisa Provez, Lien Kuchmiy, Anna Strubbe, Steven Reunes, Lindy Pieters, Tim Matthijssens, Filip Van Loocke, Wouter Erarslan-Uysal, Büşra Richter-Pechańska, Paulina Declerck, Ken Lammens, Tim De Moerloose, Barbara Deforce, Dieter Van Nieuwerburgh, Filip Cheung, Laurence Kotecha, Rishi S Mansour, Marc R Ghesquière, Bart Van Camp, Guy Berghe, Wim Vanden Kowalczyk, Jerzy R Szczepański, Tomasz Davé, Utpal P Kulozik, Andreas E Goossens, Steven Curtis, David J Taghon, Tom Dawidowska, Małgorzata Degerman, Sofie Van Vlierberghe, Pieter |
| author_facet | Roels, Juliette Thénoz, Morgan Szarzyńska, Bronisława Landfors, Mattias De Coninck, Stien Demoen, Lisa Provez, Lien Kuchmiy, Anna Strubbe, Steven Reunes, Lindy Pieters, Tim Matthijssens, Filip Van Loocke, Wouter Erarslan-Uysal, Büşra Richter-Pechańska, Paulina Declerck, Ken Lammens, Tim De Moerloose, Barbara Deforce, Dieter Van Nieuwerburgh, Filip Cheung, Laurence Kotecha, Rishi S Mansour, Marc R Ghesquière, Bart Van Camp, Guy Berghe, Wim Vanden Kowalczyk, Jerzy R Szczepański, Tomasz Davé, Utpal P Kulozik, Andreas E Goossens, Steven Curtis, David J Taghon, Tom Dawidowska, Małgorzata Degerman, Sofie Van Vlierberghe, Pieter |
| author_sort | Roels, Juliette |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T11:18:56Z |
| format | Journal Article |
| id | curtin-20.500.11937-81750 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| language | eng |
| last_indexed | 2025-11-14T11:18:56Z |
| publishDate | 2020 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-817502021-09-28T03:47:04Z Aging of preleukemic thymocytes drives CpG island hypermethylation in T-cell acute lymphoblastic leukemia. Roels, Juliette Thénoz, Morgan Szarzyńska, Bronisława Landfors, Mattias De Coninck, Stien Demoen, Lisa Provez, Lien Kuchmiy, Anna Strubbe, Steven Reunes, Lindy Pieters, Tim Matthijssens, Filip Van Loocke, Wouter Erarslan-Uysal, Büşra Richter-Pechańska, Paulina Declerck, Ken Lammens, Tim De Moerloose, Barbara Deforce, Dieter Van Nieuwerburgh, Filip Cheung, Laurence Kotecha, Rishi S Mansour, Marc R Ghesquière, Bart Van Camp, Guy Berghe, Wim Vanden Kowalczyk, Jerzy R Szczepański, Tomasz Davé, Utpal P Kulozik, Andreas E Goossens, Steven Curtis, David J Taghon, Tom Dawidowska, Małgorzata Degerman, Sofie Van Vlierberghe, Pieter DNA methylation Decitabine T-ALL aging self-renewing thymocytes 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. 2020 Journal Article http://hdl.handle.net/20.500.11937/81750 10.1158/2643-3230.BCD-20-0059 eng fulltext |
| spellingShingle | DNA methylation Decitabine T-ALL aging self-renewing thymocytes Roels, Juliette Thénoz, Morgan Szarzyńska, Bronisława Landfors, Mattias De Coninck, Stien Demoen, Lisa Provez, Lien Kuchmiy, Anna Strubbe, Steven Reunes, Lindy Pieters, Tim Matthijssens, Filip Van Loocke, Wouter Erarslan-Uysal, Büşra Richter-Pechańska, Paulina Declerck, Ken Lammens, Tim De Moerloose, Barbara Deforce, Dieter Van Nieuwerburgh, Filip Cheung, Laurence Kotecha, Rishi S Mansour, Marc R Ghesquière, Bart Van Camp, Guy Berghe, Wim Vanden Kowalczyk, Jerzy R Szczepański, Tomasz Davé, Utpal P Kulozik, Andreas E Goossens, Steven Curtis, David J Taghon, Tom Dawidowska, Małgorzata Degerman, Sofie Van Vlierberghe, Pieter Aging of preleukemic thymocytes drives CpG island hypermethylation in T-cell acute lymphoblastic leukemia. |
| title | Aging of preleukemic thymocytes drives CpG island hypermethylation in T-cell acute lymphoblastic leukemia. |
| title_full | Aging of preleukemic thymocytes drives CpG island hypermethylation in T-cell acute lymphoblastic leukemia. |
| title_fullStr | Aging of preleukemic thymocytes drives CpG island hypermethylation in T-cell acute lymphoblastic leukemia. |
| title_full_unstemmed | Aging of preleukemic thymocytes drives CpG island hypermethylation in T-cell acute lymphoblastic leukemia. |
| title_short | Aging of preleukemic thymocytes drives CpG island hypermethylation in T-cell acute lymphoblastic leukemia. |
| title_sort | aging of preleukemic thymocytes drives cpg island hypermethylation in t-cell acute lymphoblastic leukemia. |
| topic | DNA methylation Decitabine T-ALL aging self-renewing thymocytes |
| url | http://hdl.handle.net/20.500.11937/81750 |