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AML 1/Runx 1在造血发育中起着关键作用，其功能障碍与白血病的发生密切相关。在这项研究中，白血病相关的基因组改变和翻译后修饰的这种分子的影响进行了评估，通过使用生化分析和实验，使用小鼠胚胎干细胞。与大多数导致功能破坏的白血病相关突变的情况相反，该分子的修饰残基的一些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，并将进行分析。还进行了AML 1相互作用分子的搜索作为支持方法。

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

Expression of cancer stem cell markers CD133 and CD44 in locoregional recurrence of rectal cancer.

• 发表时间: 2011-02
• 期刊: Anticancer research
• 影响因子: 2
• 作者: T. Nagata;C. Sakakura;S. Komiyama;A. Miyashita;M. Nishio;Y. Murayama;S. Komatsu;A. Shiozaki;Y. Kuriu;H. Ikoma;M. Nakanishi;D. Ichikawa;H. Fujiwara;K. Okamoto;T. Ochiai;Y. Kokuba;T. Sonoyama;E. Otsuji

RUNX3 promoter methylation in colorectal cancer: its relationship with microsatellite instability and its suitability as a novel serum tumor marker.

• 发表时间: 2010-07
• 期刊: Anticancer research
• 影响因子: 2
• 作者: M. Nishio;C. Sakakura;T. Nagata;S. Komiyama;A. Miyashita;Takuo Hamada;Yoshiaki Kuryu;H. Ikoma

Biological analysis of AML1/RUNX1 arginine-mutants by means of hematopoietic rescue experiments of Runx1-deficient mouse embryonic stem cells

通过 Runx1 缺陷型小鼠胚胎干细胞的造血拯救实验对 AML1/RUNX1 精氨酸突变体进行生物学分析

• 发表时间: 2011
• 作者: 原田結花;原田浩徳;Mizutani S
• 通讯作者: Mizutani S

Biological analysis of Runx1 mutant at arginine-methylation sites by means of in vitro differentiation experiments using mouse ES cells

使用小鼠 ES 细胞进行体外分化实验，对精氨酸甲基化位点的 Runx1 突变体进行生物学分析

• 发表时间: 2011
• 作者: Kuribayashi K;Kobune M;et al.;Mizutani S
• 通讯作者: Mizutani S