Hematology Department, Hospital Universitario de Gran Canaria Dr. Negrín, 35019 Las Palmas de Gran Canaria, Spain.
Morphology Department, Universidad de Las Palmas de Gran Canaria, 35016 Las Palmas de Gran Canaria, Spain.
Int J Mol Sci. 2023 Aug 11;24(16):12700. doi: 10.3390/ijms241612700.
V617F is the predominant driver mutation in patients with Philadelphia-negative myeloproliferative neoplasms (MPN). mutations are also frequent in clonal hematopoiesis of indeterminate potential (CHIP) in otherwise "healthy" individuals. However, the period between mutation acquisition and MPN diagnosis (known as latency) varies widely between individuals, with mutations detectable several decades before diagnosis and even from birth in some individuals. Here, we will review the current evidence on the biological factors, such as additional mutations and chronic inflammation, which influence clonal expansion and may determine why some -mutated individuals will progress to an overt neoplasm during their lifetime while others will not. We will also introduce several germline variants that predispose individuals to CHIP (as well as MPN) identified from genome-wide association studies. Finally, we will explore possible mutation screening or interventions that could help to minimize MPN-associated cardiovascular complications or even delay malignant progression.
V617F 是费城阴性骨髓增殖性肿瘤（MPN）患者的主要驱动突变。 突变在其他“健康”个体的不确定潜能的克隆性造血（CHIP）中也很常见。然而，突变获得和 MPN 诊断之间的时间（称为潜伏期）在个体之间差异很大，在一些个体中，突变可在诊断前几十年甚至从出生时检测到。在这里，我们将回顾目前关于生物学因素的证据，如额外的突变和慢性炎症，这些因素影响克隆扩张，并可能决定为什么一些 -突变个体在其一生中会进展为显性肿瘤，而另一些则不会。我们还将介绍一些从全基因组关联研究中确定的导致个体发生 CHIP（以及 MPN）的种系变异。最后，我们将探讨可能的突变筛查或干预措施，以帮助最小化 MPN 相关的心血管并发症，甚至延迟恶性进展。
