Classical myeloproliferative neoplasms (MPNs) are clonal stem cell disorders characterised by driver mutations that affect the constitutive activation of JAK-signalling. Additional mutations to an MPN-driver occur in a large number of patients and have been shown be associated with disease presentation and progression. In this review, we will outline the current hypotheses regarding how clonal evolution in MPN is thought to occur and the functional mechanisms as to how concomitant somatic mutations (i.e. mutations in genes other than the 'driver' genes) contribute to disease progression. We will discuss the definitions of high molecular risk MPN, provide an overview as to how concomitant mutations influence the clinical management of MPN and suggest how this rapidly developing genetic risk stratification can be utilised to improve clinical outcomes.

中文翻译：

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高分子风险骨髓增生性肿瘤的发病机制和管理。


经典骨髓增生性肿瘤 （MPN） 是克隆性干细胞疾病，其特征是影响 JAK 信号传导组成性激活的驱动突变。MPN 驱动因子的其他突变发生在大量患者中，并且已被证明与疾病表现和进展有关。在这篇综述中，我们将概述当前关于 MPN 克隆进化如何发生的假设，以及伴随的体细胞突变（即 “驱动”基因以外的基因突变）如何导致疾病进展的功能机制。我们将讨论高分子风险 MPN 的定义，概述伴随突变如何影响 MPN 的临床管理，并建议如何利用这种快速发展的遗传风险分层来改善临床结果。