The myeloproliferative neoplasms (MPN) polycythaemia vera, essential thrombocythaemia and primary myelofibrosis are chronic myeloid disorders associated most often with mutations in JAK2, MPL and CALR, and in some patients with additional acquired genomic lesions. Whilst the molecular mechanisms downstream of these mutations are now clearer, it is apparent that clinical phenotype in MPN is a product of complex interactions, acting between individual mutations, between disease subclones, and between the tumour and background host factors. In this review we first discuss MPN phenotypic driver mutations and the factors that interact with them to influence phenotype. We consider the importance of ongoing studies of clonal haematopoiesis, which may inform a better understanding of why MPN develop in specific individuals. We then consider how best to deploy genomic testing in a clinical environment and the challenges as well as opportunities that may arise from more routine, comprehensive genomic analysis of patients with MPN.

骨髓增殖性肿瘤 (MPN) 真性红细胞增多症、原发性血小板增多症和原发性骨髓纤维化是慢性骨髓疾病，最常与JAK2 、 MPL和CALR突变相关，并且在一些患者中存在额外的获得性基因组病变。虽然这些突变下游的分子机制现在更加清晰，但很明显，MPN 的临床表型是复杂相互作用的产物，在个体突变之间、疾病亚克隆之间以及肿瘤和背景宿主因素之间发挥作用。在这篇综述中，我们首先讨论 MPN 表型驱动突变以及与它们相互作用影响表型的因素。我们认为正在进行的克隆造血研究的重要性，这可能有助于更好地理解为什么 MPN 在特定个体中发生。然后，我们考虑如何在临床环境中最好地部署基因组测试，以及对 MPN 患者进行更常规、全面的基因组分析可能带来的挑战和机遇。