书写复杂蛋白质能够影响造血细胞的细胞命运决策和自我更新能力。虽然Scribble复合物成员在哺乳动物造血过程中具有特定的细胞功能，但它们似乎高度依赖环境。通过CRISPR/Cas9基因筛选，我们已经确定了AML中Scribble复合物相关的风险因素，包括LLGL1。尽管其在HSC自我更新中有抑制功能的报道，但LLGL1的失活证实了它在AML的增殖能力和发展中的相关作用。其功能在AML的人类和小鼠模型以及不同基因背景中得到保留。LLGL1的失活导致干细胞相关基因表达的丧失，包括HoxA基因，并在白血病干细胞区域诱导出GMP样表型。HoxA9的重新表达有助于功能和表型的恢复。综上所述，这些数据确定了LLGL1作为AML中的特定依赖和潜在靶点，并强调了其细胞类型特异性功能。©2023. 作者。

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 stem cell compartment. Re-expression of HoxA9 facilitates functional and phenotypic rescue. Collectively, these data establish LLGL1 as a specific dependency and putative target in AML and emphasizes its cell-type specific functions.© 2023. The Author(s).