Tenen Daniel G
Harvard Institutes of Medicine, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
Nat Rev Cancer. 2003 Feb;3(2):89-101. doi: 10.1038/nrc989.
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.
尽管对于转录因子调控各种分化系统的方式已有很多了解，而且许多人类癌症的一个标志是缺乏细胞分化，但将这两个过程联系起来的报道相对较少。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是如何扰乱正常细胞分化并导致癌症的。这个模型涉及到参与正常造血分化的谱系特异性转录因子。这些因子在AML中常常成为靶点——要么通过直接突变，要么受到易位蛋白的干扰。揭示这些潜在途径将改善AML的诊断和治疗，并为包括实体瘤在内的其他类型人类癌症提供一个可行的模型。
