Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY.
Semin Hematol. 2019 Apr;56(2):84-89. doi: 10.1053/j.seminhematol.2018.08.001. Epub 2018 Aug 22.
Acute myeloid leukemia (AML) was one of the first cancers to be sequenced at the level of the whole genome. Molecular profiling of AML through targeted sequencing panels and cytogenetics has become a mainstay in risk-stratifying AML patients and guiding clinicians toward optimal therapies for their patients. The extensive high-resolution genomic data generated to characterize AML have been instrumental in revealing the tremendous biological complexity of the disease, dictated in part by mutational, clonal, and epigenetic heterogeneity. This is further complicated by the antecedent nonleukemic state of clonal hematopoiesis that nevertheless is associated with an increased risk of developing a hematologic malignancy and with a greater risk of mortality from ischemic cardiovascular disease. Here in this review, we discuss developments in the field of AML biology and therapeutics, with a focus on advances in our understanding of how genetic and epigenetic determinants of AML have influenced prognostication and recent shifts in treatment paradigms, particularly within the context of precision oncology, for this highly complex group of hematologic malignancies.
急性髓系白血病（AML）是最早在全基因组水平进行测序的癌症之一。通过靶向测序panel 和细胞遗传学对 AML 进行分子谱分析已成为对 AML 患者进行风险分层和指导临床医生为患者选择最佳治疗方法的主要手段。为了对 AML 进行特征描述而生成的广泛的高分辨率基因组数据有助于揭示疾病的巨大生物学复杂性，部分原因是突变、克隆和表观遗传异质性所致。这进一步因克隆性造血的前白血病状态而变得复杂，尽管如此，它仍然与发生血液恶性肿瘤的风险增加以及因缺血性心血管疾病而导致死亡率增加相关。在这篇综述中，我们讨论了 AML 生物学和治疗学领域的进展，重点介绍了我们对 AML 的遗传和表观遗传决定因素如何影响预后以及最近在治疗模式转变方面的进展的理解，特别是在精准肿瘤学方面，因为这是一组高度复杂的血液恶性肿瘤。
