Deciphering the NPM1c epigenetic network in acute myeloid leukemogenesis

Le résumé fourni par la source

Nucleophosmin 1 (NPM1) gene encodes for a multifunctional nucleolar protein that shuttles between the nucleus and cytoplasm. NPM1 mutations are the most common genetic lesion in AML, accounting for one-third of cases, resulting in a cytoplasmic mislocalization of the protein (NPM1c). Until now, the focus on NPM1c in leukemia was predominantly centred on its cytoplasmic activities. However, we recently showed a pivotal role for NPM1c within the very core of leukemia cells – the nucleus – where it can bind to chromatin at important self-renewal-associated gene loci, such as HOXA/B and MEIS1, and can directly regulate the oncogenic transcription. Now the critical question is which other epigenetic factors cooperate with NPM1c in driving leukemic transformation. Our study delves into the exploration of potential NPM1c interacting epigenetic factors and dependencies of NPM1c AMLs based on hits derived from BioID and CRISPR screenings. The goal of this study is to expand our understanding of AML epigenetics and thereby identify molecular targets for potential new epigenetic therapies. Publication History Article published online: 10 May 2024 © 2024. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

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