Department of Hematology, Oncology, Hemostaselogy, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Aachen, Germany.
Blood Rev. 2020 Jul;42:100711. doi: 10.1016/j.blre.2020.100711. Epub 2020 May 30.
What is the role of inflammation in Myeloproliferative Neoplasms? This is currently a topic of much debate. In this review, we will discuss experimental results and basic concepts of inflammatory processes in the pathogenesis of myeloproliferative neoplasms (MPN). So, which are the players involved? First, these are the clonal hematopoietic stem cells (HSC) and their normal stem cell counterparts in the bone marrow (BM), as well as their more mature progeny in the BM and the peripheral blood (PB), including neutrophils, macrophages, erythrocytes, and platelets, but also other cell lineages. Second, these cells produce a plethora of inflammatory cytokines, such as interleukin 6 (IL6), interleukin 8 (IL8), TNF-alpha (TNFa), interferon-alpha (IFNa), and others. Third, these cells and cytokines act in concert with non-hematopoietic cells, including endothelial cells and mesenchymal stromal cells (MSCs). The latter cells, in particular GLI1 positive or leptin receptor (LepR) positive stromal cells, may become activated by the hematopoietic clone to give rise to myofibroblasts, producing excessive fibrosis in the bone marrow (myelofibrosis). Ultimately, the inflammatory and fibrotic circuit involving these three key players may lead to progression of the disease, resulting in BM failure and transformation into acute leukemia, also termed blast crisis. Here, we review the role of these three effectors in the pathogenesis of MPN.
炎症在骨髓增殖性肿瘤（MPN）中的作用是什么？这是目前争论的焦点。在这篇综述中，我们将讨论炎症过程在骨髓增殖性肿瘤（MPN）发病机制中的实验结果和基本概念。那么，涉及哪些参与者呢？首先，这些是克隆性造血干细胞（HSC）及其在骨髓（BM）中的正常干细胞对应物，以及它们在 BM 和外周血（PB）中的更成熟的祖细胞，包括中性粒细胞、巨噬细胞、红细胞和血小板，但也包括其他细胞谱系。其次，这些细胞产生大量的炎症细胞因子，如白细胞介素 6（IL6）、白细胞介素 8（IL8）、肿瘤坏死因子-α（TNFa）、干扰素-α（IFNa）等。第三，这些细胞和细胞因子与非造血细胞协同作用，包括内皮细胞和间充质基质细胞（MSCs）。后者，特别是 GLI1 阳性或瘦素受体（LepR）阳性基质细胞，可能被造血克隆激活，产生骨髓中的过度纤维化（骨髓纤维化）。最终，涉及这三个关键参与者的炎症和纤维化循环可能导致疾病的进展，导致骨髓衰竭并转化为急性白血病，也称为爆发性危机。在这里，我们回顾了这三个效应物在 MPN 发病机制中的作用。
