文章：

人类癌症分化的破坏：AML显示了方法

Disruption of differentiation in human cancer: AML shows the way

原文发布日期：2003-02-01

DOI: 10.1038/nrc989

类型: Review Article

开放获取: 否

要点：

1. Loss of differentiation is an important component in the pathogenesis of many cancers.
2. Acute myeloid leukaemia (AML) represents a salient example of a cancer that is characterized by a differentiation block.
3. Specific haematopoietic transcription factors are crucial for differentiation to particular lineages during normal differentiation, and are controlled by specific patterns of expression and protein interactions.
4. These same transcription factors are frequently disrupted in AML.
5. Some mechanisms of disruption involve the effect of fusion proteins that are generated by chromosomal translocations on haematopoietic transcription factors.
6. In other cases, in the absence of common translocations, the transcription factors themselves are mutated.
7. Characterizing these transcription-factor abnormalities has already affected classification schemes based on patient outcome.
8. These transcription-factor pathways represent important targets for therapeutic intervention.

要点翻译：

1. 分化障碍是许多癌症发病机制中的重要组成部分。
2. 急性髓系白血病（AML）是体现分化阻滞特征的典型范例。
3. 特定造血转录因子在正常分化过程中对特定谱系分化至关重要，其功能受表达模式和蛋白质相互作用的精确调控。
4. 这些转录因子在AML中常出现功能紊乱。
5. 部分紊乱机制涉及染色体易位产生的融合蛋白对造血转录因子的影响。
6. 其他情况下，即使不存在常见易位，转录因子自身也会发生突变。
7. 对这些转录因子异常特征的解析已经影响了基于患者预后的分类方案。
8. 这些转录因子通路已成为治疗干预的重要靶点。

英文摘要：

Although much is understood about the ways in which transcription factors regulate various differentiation systems, and one of the hallmarks of many human cancers is a lack of cellular differentiation, relatively few reports have linked these two processes. Recent studies of acute myeloid leukaemia (AML), however, have indicated how disruption of transcription-factor function can disrupt normal cellular differentiation and lead to cancer. This model involves lineage-specific transcription factors, which are involved in normal haematopoietic differentiation. These factors are often targeted in AML — either by direct mutation or by interference from translocation proteins. Uncovering these underlying pathways will improve the diagnosis and treatment of AML, and provide a working model for other types of human cancer, including solid tumours.

摘要翻译： 

尽管人们对转录因子如何调控各种分化系统已有较多了解，且许多人类癌症的一个共同特征是细胞分化缺失，但将这两个过程联系起来的报道却相对较少。然而，最近对急性髓系白血病（AML）的研究表明，转录因子功能的破坏如何干扰正常的细胞分化并导致癌症。该模型涉及谱系特异性转录因子，这些因子参与正常的造血分化。在AML中，这些因子常常成为靶点——要么通过直接突变，要么通过易位蛋白的干扰而被破坏。揭示这些潜在机制将有助于改善AML的诊断和治疗，并为其他类型的人类癌症（包括实体瘤）提供一个可行的研究模型。

原文链接：

Disruption of differentiation in human cancer: AML shows the way