Elucidating the role of Exportin-1 (XPO1) in NPM1c-driven acute myeloid leukemogenesis

The Nucleophosmin 1 (NPM1) gene encodes a versatile nucleolar protein that shuttles between the nucleus and cytoplasm. Mutations in NPM1 are the most prevalent genetic alteration in AML, occurring in approximately one-third of cases and leading to the protein’s mislocalization to the cytoplasm (NPM1c) through an additional nuclear export sequence (NES) at its C-terminus. Past research on NPM1c in leukemia has primarily focused on its cytoplasmic functions. However, our recent findings highlight a crucial role for NPM1c within the nucleus, where it unexpectedly binds to chromatin at key gene loci associated with self-renewal, such as HOXA/B and MEIS1, directly influencing oncogenic transcription. The key question now is why and how NPM1c binds to the chromatin. Our study focuses on NPM1c’s export protein, XPO1, which was shown to have an important role in the chromatin recruitment of NPM1c and other oncoproteins. The goal of the study is to expand the knowledge of the non-canonical functions of XPO1 on chromatin in AML and to identify potential new therapeutic strategies.

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Artikel online veröffentlicht:
09. Mai 2025