<oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd">
  <dc:source xml:lang="eng">Blood Advances</dc:source>
  <dc:format>application/pdf</dc:format>
  <dc:title xml:lang="eng">Clec12a is required for the pathogenesis of NUP98::NSD1 AML</dc:title>
  <dc:type xml:lang="deu">Text</dc:type>
  <dc:type xml:lang="deu">Wissenschaftlicher Artikel</dc:type>
  <dc:rights>http://creativecommons.org/licenses/by-nc-nd/4.0/</dc:rights>
  <dc:description xml:lang="eng">NUP98::NSD1 is one of the most recurring nucleoporin 98 (NUP98) fusions in acute myeloid leukemia (AML). NSD1-driven AML is associated with adverse outcomes and poor response to conventional treatments. However, limited studies have been done to identify new potential targets to develop better treatment approaches. The C-type lectin domain family 12, member A (CLEC12A) is a cell surface receptor that is differentially expressed in leukemic stem cells (LSCs) compared to healthy hematopoietic stem cells (HSCs). We demonstrated a strong overexpression of CLEC12A in both NUP98::NSD1 patients and murine AML cells transformed with NUP98::NSD1. To understand the role of Clec12a in NUP98::NSD1 AML, we depleted Clec12a expression in NUP98::NSD1+NRASG12D immortalized cells using the CRISPR/Cas9 approach. NUP98::NSD1+NRASG12D/Clec12a knockout cells showed higher levels of apoptosis and lower colony numbers in vitro compared to NUP98::NSD1+NRASG12D/Clec12a wildtype cells. Importantly, the deletion of Clec12a significantly reduced leukemic engraftment and prolonged survival of the NUP98::NSD1+NRASG12D murine model. Our data suggest to further explore CLEC12A as a potential target for the treatment of NUP98::NSD1 AML.</dc:description>
  <dc:subject xml:lang="eng">Myeloid Neoplasia</dc:subject>
  <dc:type xml:lang="eng">Text</dc:type>
  <dc:type xml:lang="eng">journal article</dc:type>
  <dc:identifier>doi:10.1182/bloodadvances.2024015739</dc:identifier>
  <dc:creator>Sagarajit Mohanty</dc:creator>
  <dc:creator>Fiorella Charles Cano</dc:creator>
  <dc:creator>Razif Gabdoulline</dc:creator>
  <dc:creator>Courteney K. Lai</dc:creator>
  <dc:creator>Basem Othman</dc:creator>
  <dc:creator>Harish Sudarsanam</dc:creator>
  <dc:creator>Thomas Eder</dc:creator>
  <dc:creator>Florian Grebien</dc:creator>
  <dc:creator>Daniel B. Lipka</dc:creator>
  <dc:creator>Reinhard Henschler</dc:creator>
  <dc:creator>Michael Heuser</dc:creator>
  <dc:language>eng</dc:language>
  <dc:publisher>American Society of Hematology</dc:publisher>
  <dc:date>2025</dc:date>
  <dc:rights xml:lang="eng">Copyright © 2025 American Society of Hematology.</dc:rights>
  <dc:rights xml:lang="eng">open access</dc:rights>
  <dc:type xml:lang="ita">Testo</dc:type>
  <dc:type xml:lang="ita">Articolo di rivista</dc:type>
  <dc:identifier>https://phaidra.vetmeduni.ac.at/o:4524</dc:identifier>
</oai_dc:dc>