文章：

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

原文发布日期：2007-11-01

DOI: 10.1038/nrc2253

类型: Review Article

开放获取: 否

要点：

1. Mixed lineage leukaemia (MLL) translocations define a unique group of leukaemias, which phenotypically can be defined as acute myeloid leukaemias (AML), acute lymphoblastic leukaemias (ALL) or biphenotypic (mixed lineage) leukaemias (MLL).
2. MLL is a methyltransferase that is involved in the positive regulation of Hox gene expression and methylation of histone H3 lysine residue 4 (H3K4).
3. As a result of inter-chromosomal translocations, the N terminus of MLL can be 'fused' to the C terminus of over 50 different partners, which results in the loss of the H3K4 methyl transferase domain.
4. A major group of MLL fusion partners appear to interact with the DOT1L methyltransferase that positively regulates transcription by methylation of histone H3 lysine residue 79 (H3K79).
5. MLL fusion proteins efficiently transform haematopoietic precursors to leukaemia stem cells.

要点翻译：

1. 混合谱系白血病（MLL）易位界定了一组独特的白血病类型，在表型上可表现为急性髓系白血病（AML）、急性淋巴细胞白血病（ALL）或双表型（混合谱系）白血病（MLL）。
2. MLL是一种甲基转移酶，参与Hox基因表达的正向调控以及组蛋白H3赖氨酸残基4（H3K4）的甲基化过程。
3. 由于染色体间易位，MLL的N端可与超过50种不同伙伴蛋白的C端发生"融合"，导致H3K4甲基转移酶结构域缺失。
4. 大部分MLL融合伴侣蛋白会与DOT1L甲基转移酶相互作用，后者通过催化组蛋白H3赖氨酸残基79（H3K79）甲基化正向调控转录。
5. MLL融合蛋白能高效地将造血前体细胞转化为白血病干细胞。

英文摘要：

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.

摘要翻译： 

涉及混合谱系白血病（MLL）基因的易位可识别出一类独特的急性白血病，且往往预示预后不良。MLL基因编码一种能与DNA结合的蛋白，该蛋白可使组蛋白H3第4位赖氨酸（H3K4）发生甲基化，从而正向调控包括多个Hox基因在内的基因表达。致病的MLL易位会产生MLL融合蛋白，这些蛋白丧失了H3K4甲基转移酶活性。MLL融合蛋白的一个关键特征是其能够高效地将造血细胞转化为白血病干细胞。染色质调节因子与白血病干细胞之间的联系支持了表观遗传景观是白血病及正常干细胞发育的重要组成部分。

原文链接：

MLL translocations, histone modifications and leukaemia stem-cell development