Grønbæk Kirsten, Müller-Tidow Carsten, Perini Giovanni, Lehmann Sören, Bach Treppendahl Marianne, Mills Ken, Plass Christoph, Schlegelberger Brigitte
Department of Hematology, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
Haematologica. 2012 Sep;97(9):1380-8. doi: 10.3324/haematol.2011.058305. Epub 2012 Apr 4.
Research over the past decade has confirmed that epigenetic alterations act in concert with genetic lesions to deregulate gene expression in acute myeloid leukemia and myelodysplastic syndromes. Epigenetic alterations may serve as markers of disease, and may potentially be used for classification, prognostication and to monitor minimal residual disease. In addition, we now have the capability to pharmaceutically target epigenetic modifications, and there is an urgent need for early validation of the efficacy of the drugs. Also, an improved understanding of the functionality of epigenetic modifications may further pave the road towards individualized therapy. The recent advances in biotechnology and bioinformatics provide a plethora of novel tools for characterizing the epigenome in clinical samples, but at this point the practical, clinical utility of these methodologies needs further exploration. Here, we provide the pros and cons of the currently most feasible methods used for characterizing the methylome in clinical samples, and give a brief introduction to novel approaches to sequencing that may revolutionize our abilities to characterize the genomes and epigenomes in acute myeloid leukemia and myelodysplastic syndrome patients.
过去十年的研究证实，表观遗传改变与基因损伤协同作用，导致急性髓系白血病和骨髓增生异常综合征中的基因表达失调。表观遗传改变可能作为疾病的标志物，并有可能用于疾病分类、预后评估以及监测微小残留病。此外，我们现在有能力对表观遗传修饰进行药物靶向治疗，并且迫切需要对这些药物的疗效进行早期验证。此外，对表观遗传修饰功能的深入了解可能会进一步为个体化治疗铺平道路。生物技术和生物信息学的最新进展为临床样本中表观基因组的表征提供了大量新工具，但目前这些方法的实际临床应用需要进一步探索。在此，我们阐述了目前用于临床样本甲基化组表征的最可行方法的优缺点，并简要介绍了可能彻底改变我们对急性髓系白血病和骨髓增生异常综合征患者基因组和表观基因组表征能力的新型测序方法。
