Division of Hematology and Hematologic Malignancies, University of Utah, Salt Lake City, UT, USA.
Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
Leuk Lymphoma. 2021 May;62(5):1031-1045. doi: 10.1080/10428194.2020.1856837. Epub 2020 Dec 18.
In recent years CMML has received increased attention as the most commonly observed MDS/MPN overlap syndrome. Renewed interest has occurred in part due to widespread adoption of next-generation sequencing panels that help render the diagnosis in the absence of morphologic dysplasia. Although most CMML patients exhibit somatic mutations in epigenetic modifiers, spliceosome components, transcription factors and signal transduction genes, it is increasingly clear that a small subset harbors an inherited predisposition to CMML and other myeloid neoplasms. More intriguing is the fact that the mutational spectrum observed in CMML is found in other types of myeloid leukemias, begging the question of how similar genetic backgrounds can lead to such divergent clinical phenotypes. In this review we present a contemporary snapshot of the genetic complexity inherent to CMML, explore the relationship between genotype-phenotype and present a stepwise model of CMML pathogenesis and progression.
近年来，CMML 作为最常见的 MDS/MPN 重叠综合征受到了越来越多的关注。重新引起人们的兴趣部分是由于广泛采用了下一代测序面板，这些面板有助于在没有形态发育不良的情况下做出诊断。尽管大多数 CMML 患者表现出表观遗传修饰因子、剪接体成分、转录因子和信号转导基因的体细胞突变，但越来越清楚的是，一小部分患者存在对 CMML 和其他骨髓性肿瘤的遗传易感性。更有趣的是，CMML 中观察到的突变谱存在于其他类型的髓性白血病中，这就提出了一个问题，即类似的遗传背景如何导致如此不同的临床表型。在这篇综述中，我们呈现了 CMML 固有遗传复杂性的现代快照，探讨了基因型-表型之间的关系，并提出了 CMML 发病机制和进展的逐步模型。
