physiomolecular analysis of S100A6 in leukemia with MLL/AF4

MLL/AF4 白血病中 S100A6 的生理分子分析

• 批准号: 22591051
• 负责人: INOKUCHI Kouichi
• 金额: $ 3万
• 依托单位: Nippon Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22591051/
• 关键词: MLL/AF4; S100A6; TNFα; caspase; IL24; FLT3ITD; AFF1; TNF; FLT3-D835I; 達伝子導入マウス

We showed that MLL-AF4-positive ALL cell lines are resistant to TNF-α. To examine the mechanism of resistance to TNF-α of MLL-AF4-positive leukemia, we focused on S100A6 as a possible factor. Upregulation of S100A6 expression and inhibition of the p53-caspase8-caspase 3 pathway were observed only in MLL-AF4-positive ALL cell lines in the presence of TNF-α. The effect of S100A6 on resistance to TNF-α by inhibition of the p53-caspase8-caspase 3 pathway of MLL-AF4-positive ALL cell lines were also confirmed by analysis using small interfering RNA against S100A6. This pathway was also confirmed in previously established MLL-AF4 transgenic mice. These results suggest that MLL-AF4-positive ALL escapes from TNF-α-mediated apoptosis by upregulation of S100A6 expression, followed by interfering with p53-caspase 8-caspase 3 pathway.

我们发现MLL-AF 4阳性ALL细胞系对TNF-α具有抗性。为了研究MLL-AF 4阳性白血病对TNF-α耐药的机制，我们将S100 A6作为一个可能的因素。在TNF-α存在下，仅在MLL-AF 4阳性ALL细胞系中观察到S100 A6表达上调和p53-caspase 8-caspase 3通路抑制。S100 A6通过抑制MLL-AF 4阳性ALL细胞系的p53-caspase 8-caspase 3途径对TNF-α抗性的影响也通过使用针对S100 A6的小干扰RNA进行分析得到证实。该途径也在先前建立的MLL-AF 4转基因小鼠中得到证实。这些结果表明，MLL-AF 4阳性ALL通过上调S100 A6表达，随后干扰p53-caspase 8-caspase 3途径逃避TNF-α介导的凋亡。

项目成果

Importance of c-kit mutation detection method sensitivity in prognostic analyses of t(8;21)(q22;q22) acute myeloid leukemia

• DOI: 10.1038/leu.2011.104
• 发表时间: 2011-09
• 期刊: Leukemia
• 影响因子: 11.4
• 作者: S. Wakita;H. Yamaguchi;Koichi Miyake;Y. Mitamura;F. Kosaka;Kazuo Dan;K. Inokuchi

Gene Therapy of Acute Lymphoblastic Leukemia with MLL/AF4 Using AAV8-IL24.

使用 AAV8-IL24 通过 MLL/AF4 进行急性淋巴细胞白血病的基因治疗。

• 发表时间: 2010
• 作者: Tamai;H.
• 通讯作者: H.

Importance of maintaining the relative dose intensity of CHOP-like regimens combined with rituximab in patients with diffuse large B-cell lymphoma

• DOI: 10.1007/s00277-010-0956-7
• 发表时间: 2010-09-01
• 期刊: ANNALS OF HEMATOLOGY
• 影响因子: 3.5
• 作者: Hirakawa, Tsuneaki;Yamaguchi, Hiroki;Dan, Kazuo
• 通讯作者: Dan, Kazuo

The prognostic impact of FLT3 mutations in acute promyelocytic leukemia

FLT3突变对急性早幼粒细胞白血病预后的影响

• 发表时间: 2012
• 作者: Hirakawa T;et al
• 通讯作者: et al

Analysis of JAK2/MPL mutations and clinical features among myeloproliferative neoplasms in Japan

日本骨髓增生性肿瘤JAK2/MPL突变及临床特征分析

• 发表时间: 2012
• 作者: Okabe M;et al
• 通讯作者: et al