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Epigenome profiling reveals an aberrant DNA methylation signature in GATA2 deficiency

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GATA2 deficiency is a complex multi-system disorder with high risk of developing myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) with a nearly complete lifetime penetrance1, 2. GATA2 carriers show a highly variable expressivity, with some individuals developing early-onset MDS, while others, remaining asymptomatic throughout life. Although no prognostic biomarkers exist, it is likely that both cooperating genetic and epigenetic drivers shape the course of the disease3. Despite advances in the identification of recurrent somatic mutations in a set of leukemia driver genes (i.e. STAG2, SETBP1, ASXL1 and ETV6), there are major gaps in understanding the molecular mechanisms associated with leukemic progression in GATA2 carriers4. Moreover, DNA methylation alterations contribute to the initiation and expansion of leukemic clones and aberrant hypermethylation occurs in adult patients with MDS and AML5, 6. However, to date, a genome-wide DNA methylome analysis in GATA2 patients has not been performed.

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MARIN-BEJAR, Oskar, ROMERO MOYA, Damià, RODRÍGUEZ UBREVA, Javier, DISTEFANO, Maximiliano, LESSI, Francesca, ARETINI, Paolo, LIQUORI, Alessandro, CASTAÑO, Julio, KOZYRA, Emilia, KOTMAYER, Lili, BUENO, Clara, CERVERA, José, RODRIGUEZ-GALLEGO, José carlos, NOMDEDÉU GUINOT, Josep francesc, MURILLO-SANJUÁN, Laura, DÍAZ DE HEREDIA, Cristina, PÉREZ-MARTÍNEZ, Antonio, LÓPEZ-CARDENAS, Félix, MARTÍNEZ-LAPERCHE, Carolina, DORADO-HERRERO, Nieves, MARCO, Francisco m., PRÓSPER, Felipe, MENENDEZ, Pablo, VALCÁRCEL, David, BALLESTAR TARÍN, Esteban, BÖDÖR, Csaba, BIGAS SALVANS, Anna, CATALÀ, Albert, WLODARSKI, Marcin w, GIORGETTI, Alessandra. Epigenome profiling reveals an aberrant DNA methylation signature in GATA2 deficiency. _Haematologica_. 2023. [consulta: 8 de gener de 2026]. ISSN: 0390-6078. [Disponible a: https://hdl.handle.net/2445/193572]

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