Philadelphia chromosome-negative chronic myeloproliferative neoplasms (MPNs) arise due to acquired somatic driver mutations in stem cells and develop over 10–30 years from the earliest cancer stages (essential thrombocythemia, polycythemia vera) towards the advanced myelofibrosis stage with bone marrow failure. TheJAK2V617Fmutation is the most prevalent driver mutation. Chronic inflammation is considered to be a major pathogenetic player, both as a trigger of MPN development and as a driver of disease progression. Chronic inflammation in MPNs is characterized by persistent connective tissue remodeling, which leads to organ dysfunction and ultimately, organ failure, due to excessive accumulation of extracellular matrix (ECM). Considering that MPNs are acquired clonal stem cell diseases developing in an inflammatory microenvironment in which the hematopoietic cell populations are progressively replaced by stromal proliferation—“a wound that never heals”—we herein aim to provide a comprehensive review of previous promising research in the field of circulating ECM fragments in the diagnosis, treatment and monitoring of MPNs. We address the rationales and highlight new perspectives for the use of circulating ECM protein fragments as biologically plausible, noninvasive disease markers in the management of MPNs.
费城染色体阴性慢性骨髓增殖性肿瘤（MPNs）源于干细胞获得性体细胞驱动突变，从早期癌症阶段（原发性血小板增多症、真性红细胞增多症）向伴有骨髓衰竭的晚期骨髓纤维化阶段发展，病程长达10至30年。其中JAK2V617F突变是最常见的驱动突变。慢性炎症被认为是MPNs发病机制中的关键因素，既是疾病发生的诱因，也是推动疾病进展的动力。MPNs中的慢性炎症以持续性结缔组织重塑为特征，由于细胞外基质（ECM）过度积累导致器官功能障碍，最终引发器官衰竭。鉴于MPNs是在炎症微环境中发展的获得性克隆干细胞疾病——造血细胞群逐渐被基质增殖所取代，形成“永不愈合的伤口”——本文旨在系统综述循环ECM片段在MPNs诊断、治疗及监测领域既往具有前景的研究成果，阐述其应用原理，并重点探讨循环ECM蛋白片段作为生物学上合理、非侵入性的疾病标志物在MPNs管理中的新前景。
肿瘤(癌症)患者之家