Mutant SETBP1 enhances NRAS-driven MAPK pathway activation to promote aggressive leukemia. Mutant SETBP1 enhances NRAS-driven MAPK pathway activation to promote aggressive leukemia

Mutations in SET binding protein 1 (SETBP1) are associated with poor outcomes in myeloid leukemias. In the Ras-driven leukemia, juvenile myelomonocytic leukemia, SETBP1 mutations are enriched in relapsed disease. We demonstrate that SETBP1 enhances the NRAS gene expression signature, driving upregulation of mitogen-activated protein kinase (MAPK) signaling and downregulation of differentiation pathways. Overall design: Comparison of gene expression in mouse bone marrow cells retrovirally expressing mutant SETBP1 and/or NRAS

SET结合蛋白1（SET binding protein 1，SETBP1）的突变与髓系白血病的不良预后密切相关。在Ras驱动型白血病——青少年粒单核细胞白血病中，SETBP1突变在复发病例中显著富集。本研究证实，SETBP1可增强NRAS基因的表达特征，驱动丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）信号通路的上调，并下调分化相关通路的表达。实验整体设计：对比经逆转录病毒介导表达突变型SETBP1和/或NRAS的小鼠骨髓细胞的基因表达谱。