Department of Haematological Medicine, King's College London, London, UK.
FEBS Lett. 2011 Jul 7;585(13):2100-11. doi: 10.1016/j.febslet.2011.03.068. Epub 2011 Apr 6.
Identification of transcription factors as prevalent targets affected by recurring chromosomal translocations has provided the first hint for the importance of transcriptional deregulation in haematological malignancies. However, the actual molecular functions of these leukaemia-associated transcription factors on gene expression remained largely unknown until the recent discovery of their association with specific enzymatic activities that modify epigenetic codes (at DNA and/or histone levels) of downstream transcriptional targets. Intriguingly, while only just about half of acute leukaemia associates with recurring translocations, emerging evidence indicates that cryptic mutations identified in the "normal-karyotype" leukaemia also frequently affect components of epigenetic machinery. We will review these recent findings and discuss their implications in understanding the biology of the disease and in development of effective cancer therapeutics.
鉴定转录因子作为受反复染色体易位影响的常见靶点,为转录失调在血液恶性肿瘤中的重要性提供了第一个线索。然而,直到最近发现这些与特定酶活性相关的白血病相关转录因子与下游转录靶点的表观遗传密码(在 DNA 和/或组蛋白水平上)的关联,这些白血病相关转录因子对基因表达的实际分子功能在很大程度上仍然未知。有趣的是,虽然只有大约一半的急性白血病与反复易位有关,但新出现的证据表明,在“正常核型”白血病中发现的隐匿性突变也经常影响表观遗传机制的组成部分。我们将回顾这些最新发现,并讨论它们在理解疾病生物学和开发有效癌症治疗方法中的意义。