Duncavage E J, Tandon B
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
Int J Lab Hematol. 2015 May;37 Suppl 1:115-21. doi: 10.1111/ijlh.12361.
Myeloid malignancies including acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are a heterogeneous group of disorders that share a common biology and are a major source of morbidity and mortality. In the last several years, studies using next-generation sequencing (NGS) have identified a core set of recurrently mutated myeloid malignancy genes in the majority of patients with AML and MDS, including those with normal cytogenetics. DNA-level mutations in several of these genes including NPM1, FLT3, and CEBPA in AML and ASXL1, ETV6, EZH2, RUNX1, and TP53 in MDS are associated with changes in patient outcomes and are now tested for in clinical laboratories. In addition to providing prognostic information, these gene mutations can be used to monitor patient disease burden through the use of ultrasensitive detection techniques. In this review, we will focus on the clinical utility of various NGS-based methods including whole-genome sequencing, exome sequencing, and targeted panel-based sequencing in the initial diagnosis and management of AML and MDS and cover recent methodological advances for the molecular monitoring of AML and MDS.
髓系恶性肿瘤，包括急性髓系白血病（AML）和骨髓增生异常综合征（MDS），是一组异质性疾病，它们具有共同的生物学特性，是发病和死亡的主要原因。在过去几年中，使用下一代测序（NGS）的研究已经在大多数AML和MDS患者中，包括那些细胞遗传学正常的患者中，鉴定出一组核心的反复突变的髓系恶性肿瘤基因。AML中的一些基因（包括NPM1、FLT3和CEBPA）以及MDS中的ASXL1、ETV6、EZH2、RUNX1和TP53的DNA水平突变与患者预后的改变相关，现在临床实验室会对这些基因进行检测。除了提供预后信息外，这些基因突变还可通过使用超灵敏检测技术来监测患者的疾病负担。在这篇综述中，我们将重点关注各种基于NGS的方法，包括全基因组测序、外显子组测序和基于靶向基因panel的测序在AML和MDS的初始诊断和管理中的临床应用，并介绍AML和MDS分子监测的最新方法进展。
