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<dc:title xml:lang="en">DEK::NUP214 acts as an XPO1-dependent transcriptional activator of essential leukemia genes</dc:title>

  
<dc:description xml:lang="en">The t(6;9)(p22.3;q34.1) translocation/DEK::NUP214 fusion protein defines a distinct subgroup of younger AML patients classified as a separate disease entity by the World Health Organization. DEK is a nuclear factor with multifunctional roles, including gene regulation, while its fusion partner, NUP214, plays a pivotal role in nuclear export by interacting with transport receptors such as XPO1. However, the precise mechanism by which DEK::NUP214 drives leukemia remains unclear. A comprehensive multi-omics comparison of 57 AML primary samples (including whole genome sequencing, targeted sequencing, transcriptomics, and drug screening with &gt;500 compounds) revealed that t(6;9) cases display a selective response to XPO1 inhibitors (Selinexor &amp; Eltanexor) and a distinct transcriptomic signature characterized by the overexpression of FOXC1 and HOX genes that are key leukemia mediators. CUT&amp;RUN experiments demonstrated the direct binding of DEK::NUP214 to the promoters of FOXC1 and HOXA/B clusters. Strikingly, the expression of these genes and the binding of DEK::NUP214 to their regulatory regions were selectively reduced upon XPO1 inhibition in t(6;9) cells. Altogether, these results identified a novel function of DEK::NUP214 as an XPO1-dependent transcriptional activator of key leukemia drivers and provide a rationale to explore the use of XPO1 inhibitors in this patient population.</dc:description>

  
<dc:identifier rdf:resource="https://phaidra.vetmeduni.ac.at/o:4612"></dc:identifier>

  
<dc:language>en</dc:language>

  
<edm:type>TEXT</edm:type>

  
<dc:type>journal article</dc:type>

  
<dc:type>Wissenschaftlicher Artikel</dc:type>

  
<dc:type>Articolo di rivista</dc:type>

  
<dc:type xml:lang="de">Text</dc:type>

  
<dc:type xml:lang="de">Wissenschaftlicher Artikel</dc:type>

  
<dc:type xml:lang="it">Testo</dc:type>

  
<dc:type xml:lang="it">Articolo di rivista</dc:type>

  
<dc:type xml:lang="en">Text</dc:type>

  
<dc:type xml:lang="en">journal article</dc:type>

  
<dc:subject xml:lang="en">Acute Myeloid Leukaemia</dc:subject>

  
<dc:subject xml:lang="en">Oncogenes</dc:subject>

  
<dcterms:issued>2025</dcterms:issued>

  
<dc:date>2025</dc:date>

  
<dc:creator>Fadimana Kaya</dc:creator>

  
<dc:creator>Findlay Bewicke-Copley</dc:creator>

  
<dc:creator>Juho Miettinen</dc:creator>

  
<dc:creator>Pedro Izquierdo</dc:creator>

  
<dc:creator>Eve Leddy</dc:creator>

  
<dc:creator>Ozgen Deniz</dc:creator>

  
<dc:creator>Vincent-Philippe Lavallee</dc:creator>

  
<dc:creator>Celine Philippe</dc:creator>

  
<dc:creator>Jiexin Zheng</dc:creator>

  
<dc:creator>Florian Grebien</dc:creator>

  
<dc:creator>Naeem Khan</dc:creator>

  
<dc:creator>Szilvia Krizsán</dc:creator>

  
<dc:creator>Joseph Saad</dc:creator>

  
<dc:creator>Alexis Nolin-Lapalme</dc:creator>

  
<dc:creator>Josee Hebert</dc:creator>

  
<dc:creator>Sebastien Lemieux</dc:creator>

  
<dc:creator>Eric Audemard</dc:creator>

  
<dc:creator>Janet Matthews</dc:creator>

  
<dc:creator>Marianne Grantham</dc:creator>

  
<dc:creator>Doriana Di Bella</dc:creator>

  
<dc:creator>Krister Wennerberg</dc:creator>

  
<dc:creator>Alun Parsons</dc:creator>

  
<dc:creator>John G. Gribben</dc:creator>

  
<dc:creator>James D. Cavenagh</dc:creator>

  
<dc:creator>S. D. Freeman</dc:creator>

  
<dc:creator>Csaba Bodor</dc:creator>

  
<dc:creator>Guy Sauvageau</dc:creator>

  
<dc:creator>Jun Wang</dc:creator>

  
<dc:creator>Pilar Llamas-Sillero</dc:creator>

  
<dc:creator>Jean-Baptiste Cazier</dc:creator>

  
<dc:creator>David C. Taussig</dc:creator>

  
<dc:creator>Dominique Bonnet</dc:creator>

  
<dc:creator>Pedro R. Cutillas</dc:creator>

  
<dc:creator>Caroline A. Heckman</dc:creator>

  
<dc:creator>Jude Fitzgibbon</dc:creator>

  
<dc:creator>Kevin Rouault-Pierre</dc:creator>

  
<dc:creator>Ana Rio-Machin</dc:creator>

  
<dc:publisher>Springer</dc:publisher>

  
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