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• W3143674029 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 example of an epigenetic hit cooperating with a genetic hit in the pathogenesis of AML." @default.
• W3143674029 created "2021-04-13" @default.
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• W3143674029 date "2021-04-08" @default.
• W3143674029 modified "2023-10-14" @default.
• W3143674029 title "Allele-specific expression of <i>GATA2</i> due to epigenetic dysregulation in <i>CEBPA</i> double-mutant AML" @default.
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• W3143674029 doi "https://doi.org/10.1182/blood.2020009244" @default.
• W3143674029 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8489178" @default.
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• W3143674029 hasPublicationYear "2021" @default.
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