Myc増強剤のクラスターは,正常および白血病の血液形成幹細胞の階層を調節する
Carsten Bahr1,2,3, Lisa von Paleske1,2,3, Veli V Uslu4
1Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Nature
|January 18, 2018
まとめ
Myc遺伝子の発現を制御する重要な規制領域は,正常な血液細胞の発達と骨髄性白血病の維持に不可欠です. 幹細胞の機能と病気の進行に影響します
科学分野:
- * 分子生物学
- * 血液学
- * 癌の生物学
背景:
- * 転写因子Mycは,血液形成性幹細胞 (HSC) と祖先細胞にとって不可欠であり,血液がんに関与しています.
- * Myc の下流にある保存された"超強化"領域は,その発現を調節する.
- * Myc 調節を理解することは,HSC 機能と白血病の治療に不可欠です.
研究 の 目的:
- * Myc発現を調節する下流の"超強化剤"の機能を調査する.
- * 正常な血液形成と白血病におけるこの調節領域の役割を決定する.
- * ヒト白血病におけるこの領域の潜在的治療標的を調査する.
主な方法:
- * Myc発現と血液形成現象を評価するためにマウスモデルでの遺伝子消去研究.
- * 強化モジュールと転写因子採用の分析
- * ヒト急性骨髄性白血病 (AML) 細胞におけるクロマチンアクセシビリティアッセイ
主要な成果:
- * "スーパーエンハンスター"領域の削除により,マウスのHSCと祖先のMyc発現がなくなり,発達障害を引き起こした.
- * この領域は"血液増強剤群" (BENC) と呼ばれ,Mycレベルを制御する複数のモジュールで構成されています.
- * BENCはMLL- AF9誘発のマウス白血病に不可欠であり,ヒトAML幹細胞のアクセシビリティが変化し,MYC発現と患者のアウトカムと相関しています.
結論:
- * 血液増強剤クラスター (BENC) は,結合増強剤の活性によってMyc発現を正確に制御する.
- * BENCは正常な血液形成と白血病幹細胞の維持に不可欠です.
- * BENCの調節不全は白血病の発生に寄与し,ヒトAMLの治療標的となる可能性があります.
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