Transcriptional Dysregulation in Abnormal Hematopoiesis and Leukemia

转录因子AML1/Runx1在造血发育中起关键作用，其功能障碍与白血病发生密切相关。在本研究中，利用小鼠胚胎干细胞进行生化分析和实验，评估了白血病相关基因组改变和该分子翻译后修饰的影响。与大多数导致功能破坏的白血病相关突变相反，该分子修饰残基的一些突变保留了其生物活性。目前正在生成这些突变的突变小鼠系，并将进行分析。寻找相互作用的AML1分子也作为一种支持方法进行。

Transcription factor, AML1/Runx1, plays a pivotal role in hematopoietic development, and its dysfunction is closely related to leukemogenesis. In this study, the influence of leukemia-associated genomic alterations and post-translational modifications of this molecule were evaluated by use of biochemical analysis and experiments using mouse embryonic stem cells. In contrast to most cases of the leukemia-associated mutations that resulted in functional disruption, some mutants for modification residues of this molecule retained its biological activity. Mutant mouse lines for those mutations were currently being generated, and will be analyzed. A search for interacting molecules of AML1 was also performed as a supporting approach.