Molecular mechanism of MLL mutant-induced MDS

MLL突变体诱导MDS的分子机制

• 批准号: 23591367
• 负责人: SASHIDA Goro
• 金额: $ 3.24万
• 依托单位: Chiba University
• 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-23591367/
• 关键词: MLL-PTD; RUNX1; 骨髄異形成症候群; 急性骨髄性白血病; 国際情報交換; MDS; エピジェネティクス; 造血幹細胞

Given that MLL-PTD regulates the expression of RUNX1 mutants at protein level, we generated a novel MDS/AML mouse model by utilizing MLL-PTD knock-in mouse and Runx1 heterozygous mouse or RUNX1 mutants. We also demonstrated how MLL-PTD and RUNX1 mutants collaborated to induce the development of MDS and promote AML following MDS.

鉴于MLL-PTD在蛋白质水平上调节RUNX1突变体的表达，我们利用MLL-PTD敲入小鼠和Runx1杂合小鼠或RUNX1突变体生成了新的MDS/AML小鼠模型。 我们还展示了 MLL-PTD 和 RUNX1 突变体如何合作诱导 MDS 的发展并促进 MDS 后的 AML。

项目成果

Concurrent loss of Ezh2 and Tet2 cooperates in the pathogenesis of myelodysplastic disorders.

• DOI: 10.1084/jem.20131144
• 发表时间: 2013-11-18
• 期刊: The Journal of experimental medicine
• 作者: Muto T;Sashida G;Oshima M;Wendt GR;Mochizuki-Kashio M;Nagata Y;Sanada M;Miyagi S;Saraya A;Kamio A;Nagae G;Nakaseko C;Yokote K;Shimoda K;Koseki H;Suzuki Y;Sugano S;Aburatani H;Ogawa S;Iwama A
• 通讯作者: Iwama A

Loss of Ezh2 Promotes the Development of Mutant-RUNX1 Induced MDS

Ezh2 缺失促进突变体 RUNX1 诱导的 MDS 的发展

• 发表时间: 2012
• 作者: Sashida G;Tanaka S;et al.
• 通讯作者: et al.

Ezh2 loss accelerates JAK2V617F-driven primary myelofibrosis.

Ezh2 缺失会加速 JAK2V617F 驱动的原发性骨髓纤维化。

• 发表时间: 2014
• 作者: Sashida G,Tomioka T;Wang C;Shide K;Shimoda K;Iwama A
• 通讯作者: Iwama A

Modeling MLL-PTD Related Myelodysplastic Syndromes in Mouse

小鼠 MLL-PTD 相关骨髓增生异常综合征建模

• 发表时间: 2012
• 作者: Xiaomei Yan;Yue Zhang;Goro Sashida;Aili Chen;Xinghui Zhao;Susan Whitman;Qianfei Wang;Michael A. Caligiuri;Zhijian Xiao;and Gang Huang
• 通讯作者: and Gang Huang

The ability of MLL to bind RUNX1 and methylate...

MLL 结合 RUNX1 和甲基化的能力...

• 发表时间: 2011
• 期刊: Blood
• 影响因子: 20.3
• 作者: Huang G;Zhao X;Wang L;et al.
• 通讯作者: et al.