Section of Medicine/Hematology/Oncology, The University of Chicago, Chicago, IL, USA.
1] Section of Medicine/Hematology/Oncology, The University of Chicago, Chicago, IL, USA [2] The University of Chicago Comprehensive Cancer Center, The University of Chicago, Chicago, IL, USA.
Leukemia. 2014 Sep;28(9):1765-73. doi: 10.1038/leu.2014.163. Epub 2014 May 20.
The importance of epigenetic aberrations in the pathogenesis of leukemias has been revealed by recurrent gene mutations that highlight epigenetic pathways as well as by the clinical success of therapies like 5-azacytidine and decitabine that work through epigenetic mechanisms. However, precise mechanisms of how gene mutations lead to leukemias and how epigenetic therapies induce clinical remissions are elusive. Current scientific inquiries that take advantage of techniques that can distinguish among the various covalent cytosine modifications at single base resolution are likely to shed light on the ways epigenetic pathways drive leukemogenesis as well as how the hypomethylating drugs induce clinical remissions. The hope is that these studies will also reveal which patients are likely to respond to epigenetic therapies. Thus, the future is likely to bring a new wave of diagnostic and prognostic tools that probe the epigenomics of leukemia to help clinicians in their management of patients.
表观遗传异常在白血病发病机制中的重要性已经被反复出现的基因突变所揭示，这些基因突变突出了表观遗传途径，同时也为 5-氮杂胞苷和地西他滨等通过表观遗传机制发挥作用的治疗方法的临床成功提供了依据。然而，基因突变导致白血病的精确机制以及表观遗传治疗如何诱导临床缓解仍然难以捉摸。目前，利用能够以单碱基分辨率区分各种共价胞嘧啶修饰的技术进行的科学研究，很可能揭示表观遗传途径驱动白血病发生的方式，以及低甲基化药物如何诱导临床缓解。人们希望这些研究还能揭示哪些患者可能对表观遗传治疗有反应。因此，未来很可能会出现一波新的诊断和预后工具，这些工具将探测白血病的表观基因组学，以帮助临床医生管理患者。
