Roles for RUNX1/AML1 in DNA damage-repair pathway

RUNX1/AML1 在 DNA 损伤修复途径中的作用

• 批准号: 23591385
• 负责人: SATOH Yusuke
• 金额: $ 3.41万
• 依托单位: Kobe Shoin Women's University (2012-2013)Osaka University (2011)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591385/
• 关键词: RUNX1; MDS; AML; DNA損傷; 骨髄異形成症候群; 造血幹細胞; DNA修復

We found that the C-terminal deletion mutant of RUNX1 attenuates DNA-damage repair responses in hematopoietic stem/progenitor cells. Bone marrow cells from MDS/AML patients harboring the RUNX1-C-terminal mutation showed significantly lower levels of GADD45A expression compared with those from MDS/AML patients with wild-type RUNX1. As for this mechanism, we found that RUNX1 directly regulates the transcription of GADD45A. These results suggest Gadd45a dysfunction due to RUNX1 mutations can cause additional mutation(s) required for multi-step leukemogenesis.

我们发现RUNX1的C端缺失突变体减弱了造血干/祖细胞的DNA损伤修复反应。携带RUNX1-C末端突变的MDS/AML患者的骨髓细胞GADD45A的表达水平明显低于携带野生型RUNX1的MDS/AML患者。对于这一机制，我们发现RUNX1直接调控GADD45A的转录。这些结果表明，RUNX1突变导致的Gadd45a功能障碍可能导致多步白血病发生所需的额外突变(S)。

项目成果

Complementary regulation of early B-lymphoid differentiation by genetic and epigenetic mechanisms.

通过遗传和表观遗传机制对早期 B 淋巴分化进行补充调节。

• DOI: 10.1007/s12185-013-1424-7
• 发表时间: 2013
• 期刊: Int J Hematol.
• 作者: Yokota T;Sudo T;Ishibashi T;Doi Y;Ichii M;Orirani K;Kanakura Y.
• 通讯作者: Kanakura Y.

An anti-apoptotic molecule, Anamorsin, is essential for erythropoiesis through the regulation of cellular labile iron pool.

抗凋亡分子阿那莫辛通过调节细胞不稳定铁库对红细胞生成至关重要。

• 作者: Tanimura A;et al
• 通讯作者: et al

RUNX1 C- terminal Mutation Attenuates The DNA- damage Repair Response in Hematopoietic Stem/Progenitor Cells

RUNX1 C 端突变减弱造血干/祖细胞的 DNA 损伤修复反应

• 发表时间: 2011
• 作者: Satoh Y;Matsumura I;Tanaka H;Kanakura Y
• 通讯作者: Kanakura Y

Satb1 promotes hematopoietic stem cell differentiation toward the lymphoid lineages

Satb1促进造血干细胞向淋巴谱系分化

• 发表时间: 2011
• 作者: Satoh Y;Yokota T;Kondo M;Lai A;Kincade P;Kouro T;Iida R;Kokame K;Miyata T;Sudo T;Tanaka H;Matsumura I;Oritani K;Kohwi-Shigematsu T;Kanakura Y
• 通讯作者: Kanakura Y

C-terminal mutation of RUNX1 attenuates the DNA-damage repair response in hematopoietic stem cells

• DOI: 10.1038/leu.2011.202
• 发表时间: 2012-02
• 期刊: Leukemia
• 影响因子: 11.4
• 作者: Yusuke Satoh;I. Matsumura;Hirokazu Tanaka;H. Harada;Y. Harada;K. Matsui;Masaru Shibata;M. Mizuki-M.-Miz