Mulet-Lazaro, Roger and van Herk, Stanley and Erpelinck, Claudia and Bindels, Eric and Sanders, Mathijs A. and Vermeulen, Carlo and Renkens, Ivo and Valk, Peter and Melnick, Ari M. and de Ridder, Jeroen and Rehli, Michael and Gebhard, Claudia and Delwel, Ruud and Wouters, Bas J. (2021) Allele-specific expression of GATA2 due to epigenetic dysregulation in CEBPA double-mutant AML. BLOOD, 138 (2). pp. 160-177. ISSN 0006-4971, 1528-0020
Full text not available from this repository. (Request a copy)Abstract
Transcriptional deregulation is a central event in the development of acute myeloid leukemia (AML). To identify potential disturbances in gene regulation, we conducted an unbiased screen of allele-specific expression (ASE) in 209 AML cases. The gene encoding GATA-binding protein 2 (GATA2) displayed ASE more often than any other myeloid- or cancer-related gene. GATA2 ASE was strongly associated with CEBPA double mutations (DMs), with 95% of cases presenting GATA2 ASE. In CEBPA DM AML with GATA2 mutations, the mutated allele was preferentially expressed. We found that GATA2 ASE was a somatic event lost in complete remission, supporting the notion that it plays a role in CEBPA DM AML. Acquisition of GATA2 ASE involved silencing of 1 allele via promoter methylation and concurrent overactivation of the other allele, thereby preserving expression levels. Notably, promoter methylation was also lost in remission along with GATA2 ASE. In summary, we propose that GATA2 ASE is acquired by epigenetic mechanisms and is a prerequisite for the development of AML with CEBPA DMs. This finding constitutes a novel.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ACUTE MYELOID-LEUKEMIA; DNA METHYLATION; GENETIC ENTITY; C/EBP-ALPHA; MUTATIONS; TRANSCRIPTION; DEFICIENCY; PROGNOSIS; REVEAL; DEFINE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 Sep 2022 09:08 |
| Last Modified: | 07 Sep 2022 09:08 |
| URI: | https://pred.uni-regensburg.de/id/eprint/46762 |
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