biostudies-literatureUnknown37(10)Eifert TScribble complex proteins can influence cell fate decisions and self-renewal capacity of hematopoietic cells. While specific cellular functions of Scribble complex members are conserved in mammalian hematopoiesis, they appear to be highly context dependent. Using CRISPR/Cas9-based genetic screening, we have identified Scribble complex-related liabilities in AML including LLGL1. Despite its reported suppressive function in HSC self-renewal, inactivation of LLGL1 in AML confirms its relevant role for proliferative capacity and development of AML. Its function was conserved in human and murine models of AML and across various genetic backgrounds. Inactivation of LLGL1 results in loss of stemness-associated gene-expression including HoxA-genes and induces a GMP-like phenotype in the leukemia sLeukemia2027-2035https://www.ebi.ac.uk/biostudies/studies/S-EPMC10539176biostudies-literatureCell fate determinant Llgl1 is required for propagation of acute myeloid leukemia.PMC10539176Heuser MLane SWHorne AEndlich NBemmann FBullinger LHeidel FHEifert TBecker ALZhang QHochhaus ASiegerist FSchnoeder TMGraessle SHsu CJScholl SVasioukhin VHaas SfalseCell fate determinant Llgl1 is required for propagation of acute myeloid leukemia.Scribble complex proteins can influence cell fate decisions and self-renewal capacity of hematopoietic cells. While specific cellular functions of Scribble complex members are conserved in mammalian hematopoiesis, they appear to be highly context dependent. Using CRISPR/Cas9-based genetic screening, we have identified Scribble complex-related liabilities in AML including LLGL1. Despite its reported suppressive function in HSC self-renewal, inactivation of LLGL1 in AML confirms its relevant role for proliferative capacity and development of AML. Its function was conserved in human and murine models of AML and across various genetic backgrounds. Inactivation of LLGL1 results in loss of stemness-associated gene-expression including HoxA-genes and induces a GMP-like phenotype in the leukemia s2023-01-01T00:00:00Z2023 Oct2025-07-12T03:06:15.1Z2025-04-05T16:01:36.116ZS-EPMC105391763758726010.1038/s41375-023-02005-9