Mulet-Lazaro, Roger and van Herk, Stanley and Nuetzel, Margit and Sijs-Szabo, Aniko and Diaz, Noelia and Kelly, Katherine and Erpelinck-Verschueren, Claudia and Schwarzfischer-Pfeilschifter, Lucia and Stanewsky, Hanna and Ackermann, Ute and Glatz, Dagmar and Raithel, Johanna and Fischer, Alexander and Pohl, Sandra and Rijneveld, Anita and Vaquerizas, Juan M. and Thiede, Christian and Plass, Christoph and Wouters, Bas J. and Delwel, Ruud and Rehli, Michael and Gebhard, Claudia (2024) Epigenetic alterations affecting hematopoietic regulatory networks as drivers of mixed myeloid/lymphoid leukemia. NATURE COMMUNICATIONS, 15 (1): 5693. ISSN , 2041-1723
Full text not available from this repository. (Request a copy)Abstract
Leukemias with ambiguous lineage comprise several loosely defined entities, often without a clear mechanistic basis. Here, we extensively profile the epigenome and transcriptome of a subgroup of such leukemias with CpG Island Methylator Phenotype. These leukemias exhibit comparable hybrid myeloid/lymphoid epigenetic landscapes, yet heterogeneous genetic alterations, suggesting they are defined by their shared epigenetic profile rather than common genetic lesions. Gene expression enrichment reveals similarity with early T-cell precursor acute lymphoblastic leukemia and a lymphoid progenitor cell of origin. In line with this, integration of differential DNA methylation and gene expression shows widespread silencing of myeloid transcription factors. Moreover, binding sites for hematopoietic transcription factors, including CEBPA, SPI1 and LEF1, are uniquely inaccessible in these leukemias. Hypermethylation also results in loss of CTCF binding, accompanied by changes in chromatin interactions involving key transcription factors. In conclusion, epigenetic dysregulation, and not genetic lesions, explains the mixed phenotype of this group of leukemias with ambiguous lineage. The data collected here constitute a useful and comprehensive epigenomic reference for subsequent studies of acute myeloid leukemias, T-cell acute lymphoblastic leukemias and mixed-phenotype leukemias. Leukemias with ambiguous lineage require further characterisation. Here, the authors perform epigenomic and transcriptomic analysis of a subgroup of such leukemias with CpG Island Methylator Phenotype and propose that epigenetic dysregulation and not genetic lesions explains their mixed phenotype.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HEALTH-ORGANIZATION CLASSIFICATION; GENE-EXPRESSION PROFILES; DNA METHYLATION DYNAMICS; FACTOR 4 KLF4; LINEAGE COMMITMENT; MYELOID-LEUKEMIA; SOMATIC MUTATION; GENOME TOPOLOGY; READ ALIGNMENT; COPY NUMBER; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Immunologie Medicine > Lehrstuhl für Zahnerhaltung und Parodontologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Jan 2026 10:51 |
| Last Modified: | 26 Jan 2026 10:51 |
| URI: | https://pred.uni-regensburg.de/id/eprint/64303 |
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