Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA.
Genes (Basel). 2020 Jul 6;11(7):749. doi: 10.3390/genes11070749.
A subset of acute myeloid leukemia (AML) arises either from an antecedent myeloid malignancy (secondary AML, sAML) or as a complication of DNA-damaging therapy for other cancers (therapy-related myeloid neoplasm, t-MN). These secondary leukemias have unique biological and clinical features that distinguish them from de novo AML. Over the last decade, molecular techniques have unraveled the complex subclonal architecture of sAML and t-MN. In this review, we compare and contrast biological and clinical features of de novo AML with sAML and t-MN. We discuss the role of genetic mutations, including those involved in RNA splicing, epigenetic modification, tumor suppression, transcription regulation, and cell signaling, in the pathogenesis of secondary leukemia. We also discuss clonal hematopoiesis in otherwise healthy individuals, as well as in the context of another malignancy, and how it challenges the conventional notion of sAML/t-MN. We conclude by summarizing the current and emerging treatment strategies, including allogenic transplant, in these complex scenarios.
一组急性髓系白血病 (AML) 要么源于先前的髓系恶性肿瘤（继发性 AML，sAML），要么是其他癌症的 DNA 损伤治疗的并发症（治疗相关髓系肿瘤，t-MN）。这些继发性白血病具有独特的生物学和临床特征，与初发性 AML 不同。在过去的十年中，分子技术已经揭示了 sAML 和 t-MN 的复杂亚克隆结构。在这篇综述中，我们比较和对比了初发性 AML 与 sAML 和 t-MN 的生物学和临床特征。我们讨论了遗传突变在继发性白血病发病机制中的作用，包括涉及 RNA 剪接、表观遗传修饰、肿瘤抑制、转录调控和细胞信号传导的突变。我们还讨论了在其他健康个体以及另一种恶性肿瘤背景下的克隆性造血，以及它如何挑战 sAML/t-MN 的传统概念。最后，我们总结了这些复杂情况下的当前和新兴治疗策略，包括同种异体移植。
