Innere Medizin 2, Hämatologie und Onkologie, Universitätsklinikum Jena, 07747 Jena, Germany.
Leibniz-Institute on Aging-Fritz Lipmann Institute (FLI), 07745 Jena, Germany.
Cells. 2019 Aug 8;8(8):854. doi: 10.3390/cells8080854.
Clonal alterations in hematopoietic cells occur during aging and are often associated with the establishment of a subclinical inflammatory environment. Several age-related conditions and diseases may be initiated or promoted by these alterations. JAK2 mutations are among the most frequently mutated genes in blood cells during aging. The most common mutation within the JAK2 gene is JAK2-V617F that leads to constitutive activation of the kinase and thereby aberrant engagement of downstream signaling pathways. JAK2 mutations can act as central drivers of myeloproliferative neoplasia, a pre-leukemic and age-related malignancy. Likewise, hyperactive JAK-signaling is a hallmark of immune diseases and critically influences inflammation, coagulation and thrombosis. In this review we aim to summarize the current knowledge on JAK2 in clonal hematopoiesis during aging, the role of JAK-signaling in inflammation and lymphocyte biology and JAK2 function in age-related diseases and malignant transformation.
造血细胞中的克隆性改变发生在衰老过程中，通常与亚临床炎症环境的建立有关。几种与年龄相关的疾病可能是由这些改变引发或促进的。JAK2 突变是衰老过程中血细胞中最常突变的基因之一。JAK2 基因中最常见的突变是 JAK2-V617F，它导致激酶的组成性激活，从而导致下游信号通路的异常参与。JAK2 突变可作为骨髓增生性肿瘤的主要驱动因素，这是一种前白血病和与年龄相关的恶性肿瘤。同样，过度活跃的 JAK 信号是免疫疾病的标志，它对炎症、凝血和血栓形成有重要影响。在这篇综述中，我们旨在总结 JAK2 在衰老过程中克隆性造血中的最新知识、JAK 信号在炎症和淋巴细胞生物学中的作用以及 JAK2 在与年龄相关的疾病和恶性转化中的功能。
