Establishment of functional analysis for genes involved in NK cell tumors using normal NK cell expansion method

使用正常 NK 细胞扩增方法建立 NK 细胞肿瘤相关基因的功能分析

• 批准号: 23659194
• 负责人: SETO Masao
• 金额: $ 2.5万
• 依托单位: 愛知県がんセンター(研究所)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-23659194/
• 关键词: 血液; 悪性リンパ腫; NK細胞; ゲノム異常

In an attempt to clarify molecular mechanisms of NK cell tumor development, oligo-array CGH and expression profiling were applied. Oligo-array CGH identified two distinct minimal common deleted regions at 6q21 where the most frequent deletion was observed at the percentage of 36%(14 of 39 cases). The genes identified were PRDM1 and FOXO3 which were functionally approved by inducing expression system. Normal NK cells were know to be expanded by culturing peripheral blood mononuclear cells(PBMC) with irradiated K562-mb15-41BBL cells to one million order of magnitude. We could amplified normal NK cells to the same order of magnitude with feeder cells recovered from frozen status. This system will be useful for the functional analysis of genes involved in NK cell tumor development.

为了阐明 NK 细胞肿瘤发展的分子机制，应用了寡阵列 CGH 和表达谱。寡阵列 CGH 在 6q21 处识别出两个不同的最小常见缺失区域，其中观察到最频繁缺失的百分比为 36%（39 例中的 14 例）。鉴定出的基因是PRDM1和FOXO3，它们通过诱导表达系统得到功能认可。众所周知，通过将外周血单核细胞 (PBMC) 与受辐射的 K562-mb15-41BBL 细胞一起培养，可以将正常 NK 细胞扩增至一百万数量级。我们可以将正常 NK 细胞扩增至与从冷冻状态恢复的饲养细胞相同的数量级。该系统可用于 NK 细胞肿瘤发展相关基因的功能分析。

项目成果

Promotion and maintenance of leukemia by ERG

• DOI: 10.1182/blood-2010-11-320515
• 发表时间: 2011-04-07
• 期刊: BLOOD
• 影响因子: 20.3
• 作者: Tsuzuki, Shinobu;Taguchi, Osamu;Seto, Masao
• 通讯作者: Seto, Masao

Gene Expression Profiling of Age-Related Epstein-Barr Virus(EBV)-Associated B-Cell Lymphoproliferative Disorder Uncovers Alterations in Immune andInflammatory Genes : Possible Implications for Pathogenesis

年龄相关的 Epstein-Barr 病毒 (EBV) 相关 B 细胞淋巴细胞增殖性疾病的基因表达谱揭示了免疫和炎症基因的改变：对发病机制的可能影响

• 发表时间: 2011
• 作者: Harumi Kato;Kazuhito Yamamoto;Masao Seto
• 通讯作者: Masao Seto

Expansion of functionally defined mouse hematopoietic stem/progenitor cells by a short isoform of RUNX1/AML1

通过 RUNX1/AML1 的短亚型扩增功能明确的小鼠造血干/祖细胞

• 发表时间: 2012
• 期刊: Blood
• 影响因子: 20.3
• 作者: Tsuzuki S;Seto M.
• 通讯作者: Seto M.

International Peripheral T-cell Lymphoma Project. Natural killer cell lymphoma shares strikingly similar molecular features with a group of non-hepatosplenic・χT-cell lymphoma and is highly sensitive to a novel aurora kinase A inhibitor in vitro

国际外周T细胞淋巴瘤项目。自然杀伤细胞淋巴瘤与一组非肝脾·χT细胞淋巴瘤具有惊人相似的分子特征，并且在体外对新型极光激酶A抑制剂高度敏感。

• 发表时间: 2011
• 期刊: Leukemia
• 影响因子: 11.4
• 作者: Iqbal J;Weisenburger DD;Seto M
• 通讯作者: Seto M

Identification of FOXO3 and PRDM1 as tumor suppressor gene candidates in NK cell neoplasms by the combination of genomic and functional analyses

通过基因组和功能分析相结合，鉴定 FOXO3 和 PRDM1 作为 NK 细胞肿瘤中的候选抑癌基因

• 发表时间: 2011
• 作者: Kennosuke Karube;Masao Nakagawa;Masao Seto
• 通讯作者: Masao Seto