1 Department of Genetics, Pathology North-Sydney, St Leonards, NSW, Australia ; 2 Kolling Institute, University of Sydney, NSW, Australia.
Transl Pediatr. 2015 Apr;4(2):107-15. doi: 10.3978/j.issn.2224-4336.2015.03.06.
The classical myeloproliferative neoplasms (MPNs) are a group of clonal diseases comprising essential thrombocythaemia (ET), polycythaemia vera (PV) and primary myelofibrosis (PMF). PMF is the rarest disease sub type and has been challenging to address due to the lack of a specific genetic marker, inadequate risk identification models and a highly variable clinical course. Continuous efforts have over time, seen the inclusion of cytogenetic information in prognostic scoring models that have resulted in improved risk stratification models providing further rationale for therapeutic management. Technological advances using single nucleotide polymorphism arrays increased the detection of known and novel MPN related changes and variant detection by massively parallel sequencing provided a large scale screening tool for the multitude of somatic gene mutations that have more recently been described in MPN. Some of these mutations show an association with specific cytogenetic changes or phenotypes. While PMF occurs mainly in adults, it has also been described in paediatric cases and shows distinct histopathological, genetic and clinical features in comparison. This review provides an overview of the genomics landscape of PMF and current developments in MPN therapy.
经典骨髓增殖性肿瘤（MPN）是一组克隆性疾病，包括特发性血小板增多症（ET）、真性红细胞增多症（PV）和原发性骨髓纤维化（PMF）。PMF 是最罕见的疾病亚型，由于缺乏特异性遗传标志物、风险识别模型不足以及临床表现高度可变，一直难以解决。随着时间的推移，人们不断努力将细胞遗传学信息纳入预后评分模型中，这导致了风险分层模型的改善，为治疗管理提供了更多的依据。使用单核苷酸多态性阵列的技术进步增加了对已知和新型 MPN 相关变化的检测，而大规模平行测序的变体检测为最近在 MPN 中描述的大量体细胞基因突变提供了大规模筛查工具。其中一些突变与特定的细胞遗传学变化或表型相关。虽然 PMF 主要发生在成年人中，但也有儿科病例的描述，与成年人相比，其在组织病理学、遗传学和临床表现方面具有明显的特征。本综述概述了 PMF 的基因组景观以及 MPN 治疗的最新进展。
