Transcriptional Dysregulation in Abnormal Hematopoiesis and Leukemia

异常造血和白血病的转录失调

• 批准号: 21591214
• 负责人: OKUDA Tsukasa
• 金额: $ 2.91万
• 依托单位: Kyoto Prefectural University of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21591214/
• 关键词: 血液腫瘍学; 白血病; 転写因子; AML1; RUNX; 造血制御; 遺伝子改変マウス; 蛋白間相互作用; 翻訳後修飾; リン酸化

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.

转录因子AML1/Runx1在造血发育中发挥着关键作用，其功能障碍与白血病发生密切相关。在这项研究中，通过生化分析和小鼠胚胎干细胞实验来评估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比，该分子残基的一些修饰突变体保留了其生物活性。目前正在生成这些突变的突变小鼠品系，并将对其进行分析。作为支持方法，还进行了 AML1 相互作用分子的搜索。

项目成果

Screening interacting molecules of the hematopoiesis-associated transcription factor, Runx1/AML1.

筛选造血相关转录因子 Runx1/AML1 的相互作用分子。

• 发表时间: 2010
• 作者: Shiomi T;他
• 通讯作者: 他

Quantitative analysis of tumor-derived methylated RUNX3 sequences in the serum of gastric cancer patients.

• 发表时间: 2009-07
• 期刊: Anticancer research
• 影响因子: 2
• 作者: C. Sakakura;Takuo Hamada;Koji Miyagawa;M. Nishio;A. Miyashita;Hiroyuki Nagata;Hiroshi Ida;S. Yazumi;E. Otsuji;T. Chiba;Kosei Ito;Yoshiaki Ito

造血発生制御の今日的理解

目前对造血发育控制的认识

• 发表时间: 2010
• 期刊: 京都府立医科大学雑誌
• 作者: 横田明日美;奥田司
• 通讯作者: 奥田司

Biological analysis of AML1-arginine mutant by means of Runx1 mutant of in vitro differentiation of mouse ES cells

利用小鼠ES细胞体外分化的Runx1突变体对AML1-精氨酸突变体进行生物学分析

• 发表时间: 2011
• 作者: Mizutani S;Taniwaki M;Okuda T
• 通讯作者: Okuda T

Evaluation of the biological role for arginine methylation of RUNX1/AML1 by hematopoietic rescue experiments

通过造血拯救实验评价RUNX1/AML1精氨酸甲基化的生物学作用

• 发表时间: 2011
• 作者: Mizutani S;Taniwaki M;Okuda T
• 通讯作者: Okuda T