A critical appraisal of tools available for monitoring epigenetic changes in clinical samples from patients with myeloid malignancies
A critical appraisal of tools available for monitoring epigenetic changes in clinical samples from patients with myeloid malignancies
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DOI：
10.3324/haematol.2011.058305
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发表时间：
2012-09-01
期刊：
影响因子：
--
通讯作者：
Schlegelberger, Brigitte
中科院分区：
文献类型：
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作者：
Gronbaek, Kirsten;Mueller-Tidow, Carsten;Schlegelberger, Brigitte
过去十年的研究证实，表观遗传改变与遗传损伤共同作用，解除了急性髓系白血病和骨髓增生异常综合征的基因表达调控。表观遗传改变可作为疾病的标志，并有可能用于分类、预测和监测微小残留病。此外，我们现在有能力从药物上针对表观遗传修饰，迫切需要及早确认这些药物的疗效。此外，对表观遗传修饰功能的更好理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表征临床样本中的表观基因组提供了过多的新工具，但在这一点上，这些方法的实用和临床应用需要进一步探索。在这里，我们提供了目前最可行的方法用于确定临床样本中的甲基组的利弊，并简要介绍了新的测序方法，这些方法可能会彻底改变我们表征急性髓系白血病和骨髓增生异常综合征患者的基因组和表观基因组的能力。
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.