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<lom:langstring xml:lang="x-none">10.1182/bloodadvances.2024015739</lom:langstring>

  
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<lom:langstring xml:lang="en">Clec12a is required for the pathogenesis of NUP98::NSD1 AML</lom:langstring>

  
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<lom:langstring xml:lang="en">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.</lom:langstring>

  
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<lom:language>eng</lom:language>

  
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<lom:langstring xml:lang="en">Myeloid Neoplasia</lom:langstring>

  
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<lom:datetime>2025-11-12T09:19:00.775Z</lom:datetime>

  
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N:Mohanty;Sagarajit;
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N:Charles Cano;Fiorella;
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N:Gabdoulline;Razif;
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N:Lai;Courteney K.;
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N:Sudarsanam;Harish;
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N:Eder;Thomas;
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N:Grebien;Florian;
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N:Lipka;Daniel B.;
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N:Henschler;Reinhard;
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N:Heuser;Michael;
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