University of Veterinary Medicine Vienna Clec12a is required for the pathogenesis of NUP98::NSD1 AML 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. en TEXT journal article Wissenschaftlicher Artikel Articolo di rivista Testo Articolo di rivista Text journal article Text Wissenschaftlicher Artikel Myeloid Neoplasia 2025 2025 Sagarajit Mohanty Fiorella Charles Cano Razif Gabdoulline Courteney K. Lai Basem Othman Harish Sudarsanam Thomas Eder Florian Grebien Daniel B. Lipka Reinhard Henschler Michael Heuser American Society of Hematology