文章：

2019年骨髓纤维化：超越JAK2抑制

Myelofibrosis in 2019: moving beyond JAK2 inhibition

原文发布日期：2019-09-11

DOI: 10.1038/s41408-019-0236-2

类型: Review Article

开放获取: 是

英文摘要：

Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by ineffective clonal hematopoiesis, splenomegaly, bone marrow fibrosis, and the propensity for transformation to acute myeloid leukemia. The discovery of mutations in JAK2, CALR, and MPL have uncovered activated JAK-STAT signaling as a primary driver of MF, supporting a rationale for JAK inhibition. However, JAK inhibition alone is insufficient for long-term remission and offers modest, if any, disease-modifying effects. Given this, there is great interest in identifying mechanisms that cooperate with JAK-STAT signaling to predict disease progression and rationally guide the development of novel therapies. This review outlines the latest discoveries in the biology of MF, discusses current clinical management of patients with MF, and summarizes the ongoing clinical trials that hope to change the landscape of MF treatment.
 

摘要翻译： 

骨髓纤维化（MF）是一种骨髓增殖性肿瘤，其特征包括无效克隆性造血、脾肿大、骨髓纤维化以及向急性髓系白血病转化的倾向。JAK2、CALR和MPL基因突变的发现揭示了JAK-STAT信号通路的激活是MF的主要驱动因素，这为JAK抑制剂的应用提供了理论依据。然而，单独使用JAK抑制剂不足以实现长期缓解，且即便存在疾病修饰作用也十分有限。因此，识别与JAK-STAT信号通路协同作用机制以预测疾病进展并合理指导新型疗法研发备受关注。本综述概述了MF生物学机制的最新发现，讨论了当前MF患者的临床管理策略，并总结了旨在改变MF治疗格局的持续临床试验。

原文链接：

Myelofibrosis in 2019: moving beyond JAK2 inhibition