Group for Immunology, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, Dr Subotića 4, POB 39, 11129 Belgrade, Serbia.
Group for Molecular Oncology, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, Dr Subotića 4, POB 39, 11129 Belgrade, Serbia.
Int J Mol Sci. 2022 Jan 27;23(3):1490. doi: 10.3390/ijms23031490.
Neutrophils are an essential component of the innate immune response, but their prolonged activation can lead to chronic inflammation. Consequently, neutrophil homeostasis is tightly regulated through balance between granulopoiesis and clearance of dying cells. The bone marrow is both a site of neutrophil production and the place they return to and die. Myeloproliferative neoplasms (MPN) are clonal hematopoietic disorders characterized by the mutations in three types of molecular markers, with emphasis on Janus kinase 2 gene mutation (). The MPN bone marrow stem cell niche is a site of chronic inflammation, with commonly increased cells of myeloid lineage, including neutrophils. The MPN neutrophils are characterized by the upregulation of JAK target genes. Additionally, MPN neutrophils display malignant nature, they are in a state of activation, and with deregulated apoptotic machinery. In other words, neutrophils deserve to be placed in the midst of major events in MPN. Our crucial interest in this review is better understanding of how neutrophils die in MPN mirrored by defects in apoptosis and to what possible extent they can contribute to MPN pathophysiology. We tend to expect that reduced neutrophil apoptosis will establish a pathogenic link to chronic inflammation in MPN.
中性粒细胞是先天免疫反应的重要组成部分,但它们的过度激活会导致慢性炎症。因此,中性粒细胞的稳态通过粒细胞生成和死亡细胞清除之间的平衡来严格调节。骨髓既是中性粒细胞产生的部位,也是它们返回和死亡的地方。骨髓增生性肿瘤(MPN)是一种克隆性造血疾病,其特征是存在三种类型的分子标志物突变,其中重点是 Janus 激酶 2 基因突变()。MPN 骨髓干细胞龛位是慢性炎症的部位,通常伴有髓系细胞,包括中性粒细胞的增加。MPN 中性粒细胞的特征是 JAK 靶基因的上调。此外,MPN 中性粒细胞表现出恶性特征,处于激活状态,凋亡机制失调。换句话说,中性粒细胞应该被置于 MPN 的重大事件之中。我们对这篇综述的关键兴趣是更好地理解中性粒细胞在 MPN 中如何通过凋亡缺陷而死亡,以及它们在多大程度上可能有助于 MPN 病理生理学。我们倾向于认为,中性粒细胞凋亡减少将建立一个与 MPN 慢性炎症相关的致病联系。