混合フェノタイプ急性白血病の遺伝的基礎と細胞起源
Thomas B Alexander1,2, Zhaohui Gu3, Ilaria Iacobucci3
1Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Nature
|September 14, 2018
まとめ
混合フェノタイプ急性白血病 (MPAL) のサブタイプは,T/ミエロイドとB/ミエロイドのMPALに特異的な変化がある. これらの発見は,起源の細胞と創始病変がMPALを駆動し,将来の臨床試験に情報を提供することを明らかにします.
科学分野:
- 血液学
- 腫瘍学
- 遺伝学
背景:
- 混合フェノタイプ急性白血病 (MPAL) は,骨髄性およびリンパ性特性の高い高リスク白血病である.
- MPALは遺伝的特徴と治療上のコンセンサスが限られているため,課題を提示しています.
研究 の 目的:
- T/ミエロイド (T/M) とB/ミエロイド (B/M) の2つの主要なサブタイプを遺伝的に特徴付ける.
- MPALの免疫フェノタイプ異質性の起源とその遺伝子変異との関係を調査する.
主な方法:
- T/MとB/MMPALサブタイプの比較ゲノム分析
- 体内の遺伝子変異とその免疫フェノタイプ異質性への影響の調査.
- MPALの発達における創始病変と起源細胞の分析
主要な成果:
- T/M MPALとB/M MPALは遺伝的に異なるサブタイプである.
- B/ M MPALではZNF384の再編成が一般的であり,T/ M MPALではバイアレルWT1変異が一般的である.
- 免疫フェノタイプの異質性は体遺伝学とは独立しており,原始的な祖先に創始的な病変がある.
結論:
- MPALの血統の乱交は 細胞の起源と創始的な病変によって引き起こされ 蓄積されたゲノム変異だけではありません
- MPALは未成熟白血病のスペクトルに収まります
- MPALの治療戦略と臨床試験の 遺伝的枠組みを提供している.
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