Division of Hematologic Malignancies and Cell Therapy, Duke University Medical Center, 2400 Pratt Street, Suite 9010, Durham, NC 27710, USA.
Curr Hematol Malig Rep. 2013 Jun;8(2):149-55. doi: 10.1007/s11899-013-0161-6.
Acute myeloid leukemia (AML) is the most common acute leukemia in the USA, which despite recent advances, continues to have a high mortality rate. It is a biologically active disease characterized by numerous cytogenetic abnormalities and multiple genetic mutations. Next-generation sequencing (NGS) will perhaps not reveal all the factors that make AML a complex disease, but does have the potential to affect the diagnosis and risk stratification of AML patients and allow more personalized therapy. AML cells are easy to obtain from the patient and samples are only minimally contaminated with normal cells, which makes it an attractive cancer to study. Several studies have now demonstrated that the majority of AML patients are cytogenetically normal and the genome of these patients may contain fewer mutations than cancer genomes that are highly aneuploidy, suggesting that mutations in diploid genomes are more likely to be pathogenetically relevant. Whole-genome, exome, transcriptome, and targeted gene sequencing studies have been conducted successfully in AML and have provided with valuable information. The challenges for the future include: reducing the cost of sequencing, understanding epigenetic changes, managing data across various platforms, separating the driver mutations from the sea of passenger mutations, and finally, educating future generations to allow a better understanding and easy availability of these complex methodologies.
急性髓系白血病（AML）是美国最常见的急性白血病，尽管最近取得了进展，但死亡率仍然很高。它是一种具有生物活性的疾病，其特征是存在许多细胞遗传学异常和多种基因突变。下一代测序（NGS）可能无法揭示使 AML 成为复杂疾病的所有因素，但确实有可能影响 AML 患者的诊断和风险分层，并允许进行更个性化的治疗。AML 细胞很容易从患者中获得，并且样本仅轻微污染正常细胞，这使其成为一种有吸引力的癌症研究对象。现在有几项研究表明，大多数 AML 患者的细胞遗传学正常，这些患者的基因组可能比高度非整倍体的癌症基因组包含更少的突变，这表明二倍体基因组中的突变更可能与发病机制相关。全基因组、外显子组、转录组和靶向基因测序研究已在 AML 中成功进行，并提供了有价值的信息。未来的挑战包括：降低测序成本、了解表观遗传变化、跨多个平台管理数据、将驱动突变与乘客突变区分开，以及最终教育后代，使他们能够更好地理解和方便地使用这些复杂的方法。
