Guijarro-Hernández Ana, Vizmanos José Luis
Department of Biochemistry and Genetics, School of Sciences, University of Navarra, 31008 Pamplona, Spain.
Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain.
Cancers (Basel). 2021 Feb 26;13(5):984. doi: 10.3390/cancers13050984.
-negative myeloproliferative neoplasms (polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF)) are infrequent blood cancers characterized by signaling aberrations. Shortly after the discovery of the somatic mutations in JAK2, MPL, and CALR that cause these diseases, researchers extensively studied the aberrant functions of their mutant products. In all three cases, the main pathogenic mechanism appears to be the constitutive activation of JAK2/STAT signaling and JAK2-related pathways (MAPK/ERK, PI3K/AKT). However, some other non-canonical aberrant mechanisms derived from mutant JAK2 and CALR have also been described. Moreover, additional somatic mutations have been identified in other genes that affect epigenetic regulation, tumor suppression, transcription regulation, splicing and other signaling pathways, leading to the modification of some disease features and adding a layer of complexity to their molecular pathogenesis. All of these factors have highlighted the wide variety of cellular processes and pathways involved in the pathogenesis of MPNs. This review presents an overview of the complex signaling behind these diseases which could explain, at least in part, their phenotypic heterogeneity.
阴性骨髓增殖性肿瘤（真性红细胞增多症（PV）、原发性血小板增多症（ET）和原发性骨髓纤维化（PMF））是罕见的血液癌症，其特征为信号异常。在发现导致这些疾病的JAK2、MPL和CALR体细胞突变后不久，研究人员就广泛研究了其突变产物的异常功能。在所有这三种情况下，主要致病机制似乎都是JAK2/STAT信号通路和JAK2相关通路（MAPK/ERK、PI3K/AKT）的组成性激活。然而，也有一些源自突变JAK2和CALR的其他非经典异常机制被描述。此外，在影响表观遗传调控、肿瘤抑制、转录调控、剪接和其他信号通路的其他基因中也发现了额外的体细胞突变，这导致了一些疾病特征的改变，并为其分子发病机制增添了一层复杂性。所有这些因素都凸显了参与MPNs发病机制的细胞过程和通路的多样性。本综述概述了这些疾病背后的复杂信号，这至少可以部分解释它们的表型异质性。
