Epigenetic alterations affecting hematopoietic regulatory networks as drivers of mixed myeloid/lymphoid leukemia
22 pages, 7 figures, supplementary information https://doi.org/10.1038/s41467-024-49811-y.-- Data availability: The raw RNA-seq data of AML patients have been previously used in another study152 and are available at the European Genome-phenome Archive (EGA) under accession number EGAS00001004684. Al...
| Autores: | , , , , , , , , , , , , , , , , , , , , , |
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| Tipo de documento: | artigo |
| Estado: | Versão publicada |
| Data de publicação: | 2024 |
| País: | España |
| Recursos: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositório: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
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| Acesso em linha: | http://hdl.handle.net/10261/365728 |
| Access Level: | Acceso aberto |
| Palavra-chave: | http://metadata.un.org/sdg/3 Ensure healthy lives and promote well-being for all at all ages |
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Epigenetic alterations affecting hematopoietic regulatory networks as drivers of mixed myeloid/lymphoid leukemia |
| title |
Epigenetic alterations affecting hematopoietic regulatory networks as drivers of mixed myeloid/lymphoid leukemia |
| spellingShingle |
Epigenetic alterations affecting hematopoietic regulatory networks as drivers of mixed myeloid/lymphoid leukemia Mulet-Lazaro, Roger http://metadata.un.org/sdg/3 Ensure healthy lives and promote well-being for all at all ages |
| title_short |
Epigenetic alterations affecting hematopoietic regulatory networks as drivers of mixed myeloid/lymphoid leukemia |
| title_full |
Epigenetic alterations affecting hematopoietic regulatory networks as drivers of mixed myeloid/lymphoid leukemia |
| title_fullStr |
Epigenetic alterations affecting hematopoietic regulatory networks as drivers of mixed myeloid/lymphoid leukemia |
| title_full_unstemmed |
Epigenetic alterations affecting hematopoietic regulatory networks as drivers of mixed myeloid/lymphoid leukemia |
| title_sort |
Epigenetic alterations affecting hematopoietic regulatory networks as drivers of mixed myeloid/lymphoid leukemia |
| dc.creator.none.fl_str_mv |
Mulet-Lazaro, Roger Herk, Stanley van Nuetzel, Margit Sijs-Szabo, Aniko Díaz, Noelia Kelly, Katherine Erpelinck-Verschueren, Claudia Schwarzfischer-Pfeilschifter, Lucia Stanewsky, Hanna Ackermann, Ute Glatz, Dagmar Raithel, Johanna Fischer, Alexander Pohl, Sandra Rijneveld, Anita Vaquerizas Erdocia, Juan Manuel Thiede, Christian Plass, Christoph Wouters, Bas J. Delwel, Ruud Rehli, Michael Gebhard, Claudia |
| author |
Mulet-Lazaro, Roger |
| author_facet |
Mulet-Lazaro, Roger Herk, Stanley van Nuetzel, Margit Sijs-Szabo, Aniko Díaz, Noelia Kelly, Katherine Erpelinck-Verschueren, Claudia Schwarzfischer-Pfeilschifter, Lucia Stanewsky, Hanna Ackermann, Ute Glatz, Dagmar Raithel, Johanna Fischer, Alexander Pohl, Sandra Rijneveld, Anita Vaquerizas Erdocia, Juan Manuel Thiede, Christian Plass, Christoph Wouters, Bas J. Delwel, Ruud Rehli, Michael Gebhard, Claudia |
| author_role |
author |
| author2 |
Herk, Stanley van Nuetzel, Margit Sijs-Szabo, Aniko Díaz, Noelia Kelly, Katherine Erpelinck-Verschueren, Claudia Schwarzfischer-Pfeilschifter, Lucia Stanewsky, Hanna Ackermann, Ute Glatz, Dagmar Raithel, Johanna Fischer, Alexander Pohl, Sandra Rijneveld, Anita Vaquerizas Erdocia, Juan Manuel Thiede, Christian Plass, Christoph Wouters, Bas J. Delwel, Ruud Rehli, Michael Gebhard, Claudia |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Agencia Estatal de Investigación (España) Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72] |
| dc.subject.none.fl_str_mv |
http://metadata.un.org/sdg/3 Ensure healthy lives and promote well-being for all at all ages |
| topic |
http://metadata.un.org/sdg/3 Ensure healthy lives and promote well-being for all at all ages |
| description |
22 pages, 7 figures, supplementary information https://doi.org/10.1038/s41467-024-49811-y.-- Data availability: The raw RNA-seq data of AML patients have been previously used in another study152 and are available at the European Genome-phenome Archive (EGA) under accession number EGAS00001004684. All the other raw sequencing data derived from donors or patients have been generated in this study and are deposited at the EGA under accession number EGAS00001007094. This EGA study includes the following datasets: MCIP-seq, RNA-seq, ATAC-seq, ChIP-seq (H3K27ac, CTCF, SPI1, CEBPA, TCF7), and Hi-C. Since these data are derived from human subjects, they are only available under restricted access, which can be requested for each dataset separately on the EGA website. Requestors must sign a data access agreement outlining the terms and conditions for data use and fill in a form specifying their research question. Requests will be processed within 1 week, and the data will be available for a maximum of 2 years unless an appeal for extension is submitted. Processed data are publicly available in ArrayExpress with the following identifiers: E-MTAB-13117 (CTCF ChIP-seq), E-MTAB-13118 (ATAC-seq), E-MTAB-13119 (H3K27ac ChIP-seq), E-MTAB-13120 (MCIP-seq), E-MTAB-13121 (RNA-seq), E-MTAB-13122 (Hi-C), E-MTAB-14060 (TF ChIP-seq). The remaining data are available within the Article, Supplementary Information, and Source Data that accompany this article. In addition, we have used publicly available data from the ENCODE78 and FANTOM93 consortia, as well as a single-cell RNA-seq dataset of hematopoietic cells obtained from the Gene Expression Omnibus (GEO) database under the accession code GSE149938143. We also used Illumina Infinium MethylationEPIC data from T-ALL25 (GSE147667) and AML26 (GSE159907). Source data are provided with this paper.-- Code availability: All software tools employed in this study are freely or commercially available (see Methods). R code used in the analysis of the data presented here can be found in Supplementary Code 1 |
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2024 |
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2024 2024 2024 |
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Inglés |
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https://doi.org/10.1038/s41467-024-49811-y Sí |
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openAccess |
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Nature Publishing Group |
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Nature Publishing Group |
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Epigenetic alterations affecting hematopoietic regulatory networks as drivers of mixed myeloid/lymphoid leukemiaMulet-Lazaro, RogerHerk, Stanley vanNuetzel, MargitSijs-Szabo, AnikoDíaz, NoeliaKelly, KatherineErpelinck-Verschueren, ClaudiaSchwarzfischer-Pfeilschifter, LuciaStanewsky, HannaAckermann, UteGlatz, DagmarRaithel, JohannaFischer, AlexanderPohl, SandraRijneveld, AnitaVaquerizas Erdocia, Juan ManuelThiede, ChristianPlass, ChristophWouters, Bas J.Delwel, RuudRehli, MichaelGebhard, Claudiahttp://metadata.un.org/sdg/3Ensure healthy lives and promote well-being for all at all ages22 pages, 7 figures, supplementary information https://doi.org/10.1038/s41467-024-49811-y.-- Data availability: The raw RNA-seq data of AML patients have been previously used in another study152 and are available at the European Genome-phenome Archive (EGA) under accession number EGAS00001004684. All the other raw sequencing data derived from donors or patients have been generated in this study and are deposited at the EGA under accession number EGAS00001007094. This EGA study includes the following datasets: MCIP-seq, RNA-seq, ATAC-seq, ChIP-seq (H3K27ac, CTCF, SPI1, CEBPA, TCF7), and Hi-C. Since these data are derived from human subjects, they are only available under restricted access, which can be requested for each dataset separately on the EGA website. Requestors must sign a data access agreement outlining the terms and conditions for data use and fill in a form specifying their research question. Requests will be processed within 1 week, and the data will be available for a maximum of 2 years unless an appeal for extension is submitted. Processed data are publicly available in ArrayExpress with the following identifiers: E-MTAB-13117 (CTCF ChIP-seq), E-MTAB-13118 (ATAC-seq), E-MTAB-13119 (H3K27ac ChIP-seq), E-MTAB-13120 (MCIP-seq), E-MTAB-13121 (RNA-seq), E-MTAB-13122 (Hi-C), E-MTAB-14060 (TF ChIP-seq). The remaining data are available within the Article, Supplementary Information, and Source Data that accompany this article. In addition, we have used publicly available data from the ENCODE78 and FANTOM93 consortia, as well as a single-cell RNA-seq dataset of hematopoietic cells obtained from the Gene Expression Omnibus (GEO) database under the accession code GSE149938143. We also used Illumina Infinium MethylationEPIC data from T-ALL25 (GSE147667) and AML26 (GSE159907). Source data are provided with this paper.-- Code availability: All software tools employed in this study are freely or commercially available (see Methods). R code used in the analysis of the data presented here can be found in Supplementary Code 1Leukemias 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 leukemiasThis work was funded by grants from the following organizations: (1) Dutch Cancer Foundation: EMCR 2015-7935 (R.D.), EMCR 2015-7550 (B.W.); (2) Leukemia & Lymphoma Society (LLS), Special Fellowship in Clinical Research: Grant # 4317-16 (B.W.); (3) Deutsche Forschungsgemeinschaft SPP2202 Priority Program: GE 202/1-1 (C.G. and J.M.V); (4) Medical Research Council: UK MC_UP_1605/10 (J.M.V.); (5) the Academy of Medical Sciences and the Department of Business, Energy and Industrial Strategy: APR3\1017 (J.M.V.); (6) German Cancer Aid (M.R.); (7) Wilhelm Sander Stiftung (M.R.); (8) Krebshilfe Antrag 111602 (M.R.)With the institutional support of the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S)Peer reviewedNature Publishing GroupAgencia Estatal de Investigación (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202420242024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/365728reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttps://doi.org/10.1038/s41467-024-49811-ySíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3657282026-05-22T06:33:51Z |
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