AML1-ETOの白血病発生性は,サイト固有のリジンアセチル化に依存しています
Lan Wang1, Alexander Gural, Xiao-Jian Sun
1Molecular Pharmacology and Chemistry Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Science (New York, N.Y.)
|July 19, 2011
まとめ
AML1-ETO融合タンパク質のp300によるアセチル化は,急性骨髄性白血病 (AML) の発症に不可欠である. p300を阻害すると,このアセチル化が阻害され,AML患者にとって潜在的な治療戦略となる.
科学分野:
- 腫瘍学 腫瘍学
- 分子生物学は分子生物学である.
- 血液学 ヘマトロジ
背景:
- 急性骨髄性白血病 (AML) の染色体転位は,融合タンパク質を生成する.
- これらの融合タンパク質をターゲットにすることは困難ですが,それらの翻訳後の修正は潜在的なターゲットです.
研究 の 目的:
- AMLの病原性における翻訳後の改変の役割を調査する.
- AMLにおけるこれらの改変を標的とした治療の可能性を探求する.
主な方法:
- 患者由来白血病細胞におけるAML1-ETOアセチル化の分析.
- 人間の帯血のCD34 ((+) 細胞を用いた機能的研究.
- マウスモデルでの白血病原性分析.
- AML1-ETOアセチル化と機能への影響を評価するためにp300の抑制.
主要な成果:
- AML1-ETOは,t(8;21) AMLにおける融合タンパク質であり,p300によってアセチル化されます.
- このアセチル化は,AML1-ETOの自己再生促進と白血病原性のために不可欠です.
- p300の阻害はAML1-ETOアセチル化を防止し,白血病変異を阻害する.
結論:
- p300などのリシンアセチルトランスフェラーゼは,AMLの病原性の重要なレギュレータです.
- リジンアセチルトランスフェラーゼを標的とした治療は,AMLに対する有望な治療戦略です.
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