Ambinder Alexander J, DeZern Amy E
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Front Oncol. 2022 Oct 28;12:1033534. doi: 10.3389/fonc.2022.1033534. eCollection 2022.
Myelodysplastic syndrome and acute myeloid leukemia are heterogeneous myeloid neoplasms which arise from the accumulation of mutations in a myeloid stem cell or progenitor that confer survival or growth advantages. These disease processes are formally differentiated by clinical, laboratory, and morphological presentations, especially with regard to the preponderance of blasts in the peripheral blood or bone marrow (AML); however, they are closely associated through their shared lineage as well as their existence on a spectrum with some cases of MDS displaying increased blasts, a feature that reflects more AML-like behavior, and the propensity for MDS to transform into AML. It is increasingly recognized that the distinctions between these two entities result from the divergent patterns of genetic alterations that drive each of them. Mutations in genes related to chromatin-remodeling and the spliceosome are seen in both MDS and AML arising out of antecedent MDS, while mutations in genes related to signaling pathways such as or are more typically seen in AML or otherwise are a harbinger of transformation. In this review, we focus on the insights into the biological and genetic distinctions and similarities between MDS and AML that are now used to refine clinical prognostication, guide disease management, and to inform development of novel therapeutic approaches.
骨髓增生异常综合征和急性髓系白血病是异质性髓系肿瘤，由髓系干细胞或祖细胞中积累的突变引起，这些突变赋予生存或生长优势。这些疾病过程通过临床、实验室和形态学表现进行正式区分，特别是在外周血或骨髓中原始细胞的优势方面（AML）；然而，它们通过共同的谱系以及在一个谱系上的存在而密切相关，一些MDS病例显示原始细胞增加，这一特征反映了更类似AML的行为，以及MDS转化为AML的倾向。人们越来越认识到，这两种实体之间的区别源于驱动它们的不同基因改变模式。与染色质重塑和剪接体相关的基因中的突变在MDS和由先前MDS引起的AML中均可见，而与信号通路相关的基因中的突变，如 或 ，更典型地见于AML，或者是转化的先兆。在本综述中，我们关注对MDS和AML之间生物学和遗传学区别及相似性的见解，这些见解现在用于完善临床预后评估、指导疾病管理并为新型治疗方法的开发提供信息。
