EVI1遺伝子群によるGATA2転写制御と白血病発症機構の解析

EVI1基因组GATA2转录调控及白血病发病机制分析

• 批准号: 17014074
• 负责人: 森下 和広
• 金额: $ 3.39万
• 依托单位: University of Miyazaki
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 无数据
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17014074/
• 关键词: EVI1; GATA-2; 造血幹細胞; 白血病幹細胞; 転写因子; DNAマイクロアレイ

EVI1遺伝子は、マウス及びヒト骨髄性白血病の原因遺伝子であり転写因子である。染色体転座によりEVI1高発現した白血病は難治性白血病に属する。そのEVI1高発現白血病の病態を調べ、新しい治療法を開発する目的で、まず、Evi1 KOマウスの解析を行い、Evi1遺伝子発現と造血幹細胞の異常を検討したEVI1遺伝子は骨髄細胞中幹細胞分画に高発現をしており、マウス胎児において、卵黄嚢、大動脈近傍P-Sp領域に高発現していた。KOマウスの造血能を検討したところ、マウス胎児二次造血での、造血幹細胞数の低下、それに伴う血管新生の異常があり、受精後10.5日で出血死を引き起こすことを同定した(慶応大学・須田先生との共同研究)。さらにKOマウスにおける造血組織の遺伝子解析を行ったところ、GATA-2遺伝子が特異的に発現の低下が見られた。またDNAマイクロアレイを用いて、EVI1/MEL1高発現白血病細胞株で、EVI1遺伝子群によって転写調節される遺伝子群の単離を試みた。その結果EVI1/MEL1の発現により、3倍以上の発現亢進遺伝子群68,発現低下群93を同定した。その低下群にGATA-2が含まれていたため、EVI1欠損マウスの結果と合わせGATA-2プロモーター解析を行った。その結果、EVI1が直接的にGATA-2プロモーター領域に結合し、GATA-2遺伝子発現調節に係わっていることを同定した(EMBO J 2005)。このことにより初めてEVI1の直接の標的遺伝子を同定することができ、EVI1によるGATA-2遺伝子の調節という転写因子カスケードによる造血発生機構の第一歩が明らかになった。従ってEVI1高発現白血病細胞におけるGATA-2転写調節が白血病発症に係わっている可能性を示唆するものである。

The causes of EVI1, bone leukemia, bone leukemia and bone leukemia. Chromosomal aberration, EVI1 height, leukemia, leukemia. There is a high incidence of leukemia in EVI1, a new method for treatment of leukemia, and a new method for the treatment of leukemia. the purpose of this study is to analyze the results of the new method of treatment of leukemia. the results of Evi1 analysis and Evi1 analysis show that the cells of hematopoietic progenitor cells in the bone marrow cells of peripheral blood mononuclear cells (EVI1) are significantly higher than those of normal leukemias, pregnant women, fetus, egg yolk, and large cells near the P-Sp field. The hematopoietic energy of KO, fetal secondary hematopoiesis, low hematopoietic cell count, hematopoietic angiogenesis, haemorrhage death 10.5 days after fertilization were studied jointly by Mr. Tian of the University. The hematopoietic tissue subset of the hematopoietic tissue was analyzed in terms of KO, GATA-2, and so on. The DNA virus was used to detect leukaemia cell lines with high levels of EVI1/MEL1, and the subgroup of EVI1 cells was isolated from the virus. The results showed that the hyperactive subgroup (68) and the low group (93%) were detected in EVI1/MEL1, hyperactive subgroup and low subgroup. The results show that the GATA-2 of the low-level group contains the following information, the EVI1 is not valid, and the results are consistent with the results of the GATA-2 analysis. The result of the test, the direct combination of the field data of EVI1, and the subset of GATA-2, show that the results are the same as those of EMBO J 2005. In the first place, the first part of the hematopoietic health mechanism is the same as that of EVI1 and EVI1. The first part of the hematopoietic health mechanism is the first part of the hematopoietic system. The possibility of leukemia caused by EVI1 is high, and the possibility of leukemia is not known by writing about leukemia in GATA-2.

项目成果

Evi-1 expression in Xenopus

• DOI: 10.1016/j.modgep.2005.03.007
• 发表时间: 2005-06-01
• 期刊: GENE EXPRESSION PATTERNS
• 影响因子: 1.2
• 作者: Mead, PE;Parganas, E;Ihle, JN
• 通讯作者: Ihle, JN

Adenovirus-mediated transfer of human placental ectonucleoside triphosphate diphosphohydrolase to vascular smooth muscle cells suppresses platelet aggregation in vitro and arterial thrombus formation in vivo

• DOI: 10.1161/01.cir.0000155239.46511.79
• 发表时间: 2005-02-15
• 期刊: CIRCULATION
• 影响因子: 37.8
• 作者: Furukoji, E;Matsumoto, M;Asada, Y
• 通讯作者: Asada, Y

Overexpression of a cell adhesion molecule, TSLC1, as a possible molecular marker for acute-type adult T-cell leukemia

• DOI: 10.1182/blood-2004-03-1222
• 发表时间: 2005-02-01
• 期刊: BLOOD
• 影响因子: 20.3
• 作者: Sasaki, H;Nishikata, I;Morishita, K
• 通讯作者: Morishita, K

Oncogenic transcription factor Evi1 regulates hematopoietic stem cell proliferation through GATA-2 expression

• DOI: 10.1038/sj.emboj.7600679
• 发表时间: 2005-06-01
• 期刊: EMBO JOURNAL
• 影响因子: 11.4
• 作者: Yuasa, H;Oike, Y;Morishita, K
• 通讯作者: Morishita, K

Novel deletion spanning RCC1-like domain of RPGR in Japanese X-linked retinitis pigmentosa family.

• 发表时间: 2005-07
• 期刊: Molecular vision
• 影响因子: 2.2
• 作者: Zi-Bing Jin;Xiao-Qiang Liu;A. Uchida;R. Vervoort;K. Morishita;M. Hayakawa;A. Murakami;N. Matsumoto;N. Niikawa;N. Nao‐i