Programa de Pós-Graduação em Ciências Aplicadas à Hematologia, Universidade do Estado do Amazonas (UEA), Manaus 69850-000, AM, Brazil.
Programa de Pós-Graduação em Imunologia Básica e Aplicada, Universidade Federal do Amazonas (UFAM), Manaus 69067-005, AM, Brazil.
Biomolecules. 2022 Feb 11;12(2):291. doi: 10.3390/biom12020291.
The V617F variant constitutes a genetic alteration of higher frequency in BCR/ABL1 negative chronic myeloproliferative neoplasms, which is caused by a substitution of a G ˃ T at position 1849 and results in the substitution of valine with phenylalanine at codon 617 of the polypeptide chain. Clinical, morphological and molecular genetic features define the diagnosis criteria of polycythemia vera, essential thrombocythemia and primary myelofibrosis. Currently, V617F is associated with clonal hematopoiesis, genomic instability, dysregulations in hemostasis and immune response. V617F clones induce an inflammatory immune response and lead to a process of immunothrombosis. Recent research has shown great interest in trying to understand the mechanisms associated with V617F signaling and activation of cellular and molecular responses that progressively contribute to the development of inflammatory and vascular conditions in association with chronic myeloproliferative neoplasms. Thus, the aim of this review is to describe the main genetic, hematological and immunological findings that are linked to JAK2 variant signaling in chronic myeloproliferative neoplasms.
V617F 变体构成了 BCR/ABL1 阴性慢性骨髓增生性肿瘤中更高频率的遗传改变，它是由 1849 位核苷酸的 G ˃ T 取代引起的，导致多肽链 617 位密码子的缬氨酸被苯丙氨酸取代。临床、形态学和分子遗传学特征定义了真性红细胞增多症、原发性血小板增多症和原发性骨髓纤维化的诊断标准。目前，V617F 与克隆性造血、基因组不稳定性、止血和免疫反应失调有关。V617F 克隆诱导炎症免疫反应，并导致免疫血栓形成过程。最近的研究对试图理解与 V617F 信号转导相关的机制以及与慢性骨髓增生性肿瘤相关的炎症和血管状况的发展相关的细胞和分子反应的激活表现出极大的兴趣。因此，本综述的目的是描述与 JAK2 变体信号转导相关的慢性骨髓增生性肿瘤的主要遗传、血液学和免疫学发现。
