Determining the role of Rel/NF-kB Transcription Factors in Myeloid Differentiation

确定 Rel/NF-kB 转录因子在骨髓分化中的作用

• 批准号: nhmrc : 406651
• 负责人: Prof Steve Gerondakis
• 金额: $ 33.4万
• 依托单位: Macfarlane Burnet Institute for Medical Research and Public Health
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2006
• 资助国家: 澳大利亚
• 起止时间: 2006-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/determining-role-relnf-myeloid-differentiation/94779
• 关键词: Determining; role; Rel; NF; kB

Different types of mature blood cells arise from stem cells in a process involving changes in gene expression that dictate which types of blood cells ultimately develop. A family of gene regulatory proteins called NF-kB transcription factors has been found to control the pattern of gene expression in a particular blood cell precursor called a granulocyte macrophage precursor (GMP) that normally generates two types of mature blood cells called macrophages and neutrophils. In the absence of NF-kB proteins, a change in the pattern of gene expression in GMPs leads to an imbalance in production of these two blood cell types that now favours the generation of neutrophils. This work will provide insight into the molecular mechanisms of blood cell development regulated by NF-kB. With disturbances in the balance of blood cell formation representing a hallmark of leukemia, understanding how this process is normally controlled may have important implications for developing therapeutic strategies to combat various types of leukemias.

不同类型的成熟血细胞从干细胞中产生，这一过程涉及基因表达的变化，而基因表达的变化决定了哪种类型的血细胞最终会发育。一个被称为NF-kB转录因子的基因调节蛋白家族被发现控制一种叫做粒细胞巨噬细胞前体（GMP）的特定血细胞前体的基因表达模式，这种细胞通常产生两种类型的成熟血细胞，称为巨噬细胞和中性粒细胞。在缺乏NF-kB蛋白的情况下，gmp中基因表达模式的变化导致这两种血细胞类型的产生不平衡，现在有利于中性粒细胞的产生。这项工作将为NF-kB调控血细胞发育的分子机制提供深入的见解。血细胞形成平衡紊乱是白血病的一个标志，了解这一过程是如何正常控制的，可能对开发对抗各种类型白血病的治疗策略具有重要意义。