Hermouet Sylvie
Nantes Université, INSERM, Immunology and New Concepts in ImmunoTherapy, INCIT, UMR 1302, Nantes, France.
Laboratoire d'Hématologie, CHU Nantes, Nantes, France.
Front Oncol. 2023 May 22;13:1196817. doi: 10.3389/fonc.2023.1196817. eCollection 2023.
Knowledge on the myeloproliferative neoplasms (MPNs) - polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF) - has accumulated since the discovery of the JAK/STAT-activating mutations associated with MPNs: V617F, observed in PV, ET and PMF; and the and mutations, found in ET and PMF. The intriguing lack of disease specificity of these mutations, and of the chronic inflammation associated with MPNs, triggered a quest for finding what precisely determines that MPN patients develop a PV, ET or PMF phenoptype. The mechanisms of action of MPN-driving mutations, and concomitant mutations (, others), have been extensively studied, as well as the role played by these mutations in inflammation, and several pathogenic models have been proposed. In parallel, different types of drugs have been tested in MPNs (JAK inhibitors, interferons, hydroxyurea, anagrelide, azacytidine, combinations of those), some acting on both JAK2 and inflammation. Yet MPNs remain incurable diseases. This review aims to present current, detailed knowledge on the pathogenic mechanisms specifically associated with PV, ET or PMF that may pave the way for the development of novel, curative therapies.
自从发现与骨髓增殖性肿瘤（MPN）相关的JAK/STAT激活突变以来，人们对MPN——真性红细胞增多症（PV）、原发性血小板增多症（ET）、原发性骨髓纤维化（PMF）——的认识不断积累：在PV、ET和PMF中均观察到的V617F突变；以及在ET和PMF中发现的[具体突变1]和[具体突变2]突变。这些突变以及与MPN相关的慢性炎症缺乏疾病特异性，这引发了人们对究竟是什么决定MPN患者发展为PV、ET或PMF表型的探索。驱动MPN的突变以及伴随突变（[具体突变1]、其他突变）的作用机制已得到广泛研究，这些突变在炎症中的作用也得到了研究，并且已经提出了几种致病模型。与此同时，不同类型的药物已在MPN中进行了测试（JAK抑制剂、干扰素、羟基脲、阿那格雷、阿扎胞苷、这些药物的组合），其中一些药物对JAK2和炎症均有作用。然而，MPN仍然是无法治愈的疾病。本综述旨在介绍目前关于与PV、ET或PMF特异性相关的致病机制的详细知识，这些知识可能为开发新的治愈性疗法铺平道路。
