メニン腫瘍サプレッサータンパク質は,MLLに関連した白血病発生のための不可欠な腫瘍学的コファクターです
Akihiko Yokoyama1, Tim C P Somervaille, Kevin S Smith
1Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA.
Cell
|October 22, 2005
まとめ
腫瘍性混合血統白血病 (MLL) 融合タンパク質は,白血病発生のために腫瘍抑制剤メニンと相互作用する必要があります. メニンは,MLLによって引き起こされる骨髄膜変異と表遺伝的変異に不可欠であり,潜在的な治療標的として有効化されています.
科学分野:
- 分子生物学は分子生物学である.
- 癌生物学 癌生物学について
- エピジェネティクス エピジェネティクス
背景:
- 混合血統白血病 (MLL) タンパク質は,急性白血病に関与するヒストンメチルトランスフェラーゼです.
- MLLは,MEN1腫瘍抑制遺伝子の産物であるメンチンを含む複合体の中で機能する.
- MEN1変異は内分泌腫瘍と関連しています.
研究 の 目的:
- MLL媒介性白血病発生におけるMLL-メニン相互作用の役割を調査する.
- メニンがMLL主導の骨髄変異の維持に不可欠であるかどうかを判断する.
- MLLに関連した癌における表皮遺伝的失調におけるメニンの役割を調査する.
主な方法:
- 腫瘍性MLL融合タンパク質とメンチンの間の安定した関連性の実証.
- MLL-メニンの相互作用が白血病発生の開始における必要性の評価.
- MLLで変異した細胞への影響を観察するために,メンンの急性遺伝的除去.
主要な成果:
- 腫瘍性MLL融合タンパク質は,保存モチーフを介してメンニンと結合し,白血病発生に不可欠です.
- メニンは,MLLに関連した骨髄変異の維持に不可欠であるが,他の腫瘍遺伝子の誘発変異には欠かせない.
- メニン切除は異常なホックス遺伝子発現を逆転させ,MLL変異ブラストの腫瘍性特性を廃止する.
結論:
- ヒトの腫瘍タンパク質 (MLL融合タンパク質) は,腫瘍抑制剤 (メニン) との直接の相互作用によって,腫瘍原性の活性が決定的に依存している.
- メニンは,MLL誘発性白血病における分子療法のための検証された潜在的な標的である.
- メニンは,血液形成性がんの病原性の基礎となる変異した表遺伝子機能において中心的な役割を果たします.
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