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| Status |
Public on Mar 01, 2021 |
| Title |
Epigenetic blueprint identifies poor outcome and hypomethylating agent-responsive T-ALL subgroup |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by array
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| Summary |
Adult T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy still associated with poor outcome calling for new therapeutic options. DNA methylation landscapes of adult T-ALL remain largely uncharacterized. Here, we systematically analyzed the DNA methylation profiles of normal thymic sorted T-cell subpopulations and 143 primary adult T-ALLs as part of French GRAALL 2003-2005 trial. Our results indicated that T-ALL is epigenetically distinct from normal T-cell subpopulations and consisted of five major subtypes (C1-C5) which were either associating with co-occurring DNMT3A/IDH2 mutations (C1), TAL1 deregulation (C2), TLX3 (C3), TLX1/in cis-HOXA9 (C4) or in trans-HOXA9 (C5) overexpression. Importantly, our data identified an unexpected subset of hypermethylated T-ALL associated with poor outcome and primary therapeutic response. Using mouse xenografts, we showed that hypermethylated T-ALL samples displayed therapeutic response to the DNA hypomethylating agent, 5-Azacitidine, which significantly delayed tumor progression suggesting epigenetic-based therapies as a novel treatment option in hypermethylated T-ALL.
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| Overall design |
To assess the heterogenity among adult T-ALLs, DNA methylation landscape of 143 primary adult T-ALL samples along with 6 distinct sorted normal thymic cell types were analysed using Illumina Methylation EPIC arrays.
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| Contributor(s) |
Touzart A, Mayakonda A, Plass C, Asnafi V |
| Citation(s) |
34039737 |
| |
| Submission date |
Mar 27, 2020 |
| Last update date |
Jul 13, 2023 |
| Contact name |
Vahid Asnafi |
| Organization name |
Universite de Paris (Descartes)
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| Street address |
149 rue de Sèvres
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| City |
Paris |
| ZIP/Postal code |
75015 |
| Country |
France |
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| Platforms (1) |
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| Samples (155)
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| Relations |
| BioProject |
PRJNA615905 |
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