混合谱系白血病（MLL）易位、组蛋白修饰与白血病干细胞发育

MLL translocations, histone modifications and leukaemia stem-cell development.

作者信息

Krivtsov Andrei V, Armstrong Scott A

机构信息

Division of Haematology/Oncology, Children's Hospital, Department of Pediatric Oncology, and Harvard Medical School, Boston, Massachusetts 02115, USA.

出版信息

Nat Rev Cancer. 2007 Nov;7(11):823-33. doi: 10.1038/nrc2253.

DOI:10.1038/nrc2253

PMID:17957188

Abstract

Translocations that involve the mixed lineage leukaemia (MLL) gene identify a unique group of acute leukaemias, and often predict a poor prognosis. The MLL gene encodes a DNA-binding protein that methylates histone H3 lysine 4 (H3K4), and positively regulates gene expression including multiple Hox genes. Leukaemogenic MLL translocations encode MLL fusion proteins that have lost H3K4 methyltransferase activity. A key feature of MLL fusion proteins is their ability to efficiently transform haematopoietic cells into leukaemia stem cells. The link between a chromatin modulator and leukaemia stem cells provides support for epigenetic landscapes as an important part of leukaemia and normal stem-cell development.

摘要

涉及混合谱系白血病（MLL）基因的易位可鉴定出一组独特的急性白血病，并且常常预示着不良预后。MLL基因编码一种DNA结合蛋白，该蛋白可使组蛋白H3赖氨酸4（H3K4）发生甲基化，并正向调节包括多个Hox基因在内的基因表达。致白血病的MLL易位编码的MLL融合蛋白已丧失H3K4甲基转移酶活性。MLL融合蛋白的一个关键特征是它们能够有效地将造血细胞转化为白血病干细胞。染色质调节剂与白血病干细胞之间的联系为表观遗传格局作为白血病和正常干细胞发育的重要组成部分提供了支持。