Biology and therapeutic targeting of molecular mechanisms in MPNs.
Biology and therapeutic targeting of molecular mechanisms in MPNs.
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MPN 分子机制的生物学和治疗靶向。
DOI：
10.1182/blood.2022017416
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发表时间：
2023-04-20
期刊：
影响因子：
20.3
通讯作者：
Mullally, Ann
中科院分区：
文献类型：
--
作者：
How, Joan;Garcia, Jacqueline S.;Mullally, Ann
骨髓增生性肿瘤(MPN)是一种克隆性的造血干细胞疾病，其特征是JAK信号转导和转录激活信号。因此，JAK抑制剂已成为治疗骨髓纤维化(MF)患者的标准疗法。尽管目前批准的JAK抑制剂成功地改善了MPN相关症状，但它们并不清楚是否会显著改变MF的病程。同样，对于原发性血小板增多症和真性红细胞增多症，治疗的主要目的是降低心血管和血栓栓塞症并发症的风险，对于被认为血栓形成风险较低的患者，通常采用谨慎等待的方法。然而，对MPN生物学的更好理解导致了合理设计疗法的发展，其目标不仅是解决疾病并发症，还可能改变疾病的进程。我们回顾了阐明疾病发病机制的最新数据，并重点介绍了在多个生物水平上针对MPN的新兴治疗方法，包括JAK2突变的MPN干细胞、JAK和非JAK信号通路、突变的钙网蛋白以及炎性骨髓微环境。在过去的20年里，我们对骨髓增生性肿瘤(MPN)生物学的了解呈爆炸式增长，这种增长的知识促进了治疗的进步。由副主编Mario Cazzola介绍，这一综述系列使读者了解经典MPN的自然历史-真性红细胞增多症、原发性血小板增多症和骨髓纤维化-以及诊断、预测和治疗这些疾病的患者的方法。
Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by activated Janus kinase (JAK)–signal transducer and activator of transcription signaling. As a result, JAK inhibitors have been the standard therapy for treatment of patients with myelofibrosis (MF). Although currently approved JAK inhibitors successfully ameliorate MPN-related symptoms, they are not known to substantially alter the MF disease course. Similarly, in essential thrombocythemia and polycythemia vera, treatments are primarily aimed at reducing the risk of cardiovascular and thromboembolic complications, with a watchful waiting approach often used in patients who are considered to be at a lower risk for thrombosis. However, better understanding of MPN biology has led to the development of rationally designed therapies, with the goal of not only addressing disease complications but also potentially modifying disease course. We review the most recent data elucidating mechanisms of disease pathogenesis and highlight emerging therapies that target MPN on several biologic levels, including JAK2-mutant MPN stem cells, JAK and non-JAK signaling pathways, mutant calreticulin, and the inflammatory bone marrow microenvironment. Our knowledge about the biology of myeloproliferative neoplasms (MPNs) has exploded in the last 20 years, and this increased knowledge has led to advances in therapy. Introduced by Associate Editor Mario Cazzola, this Review Series brings readers up to date on our understanding of the natural history of the classical MPNs—polycythemia vera, essential thrombocythemia, and myelofibrosis—and the approaches to diagnosis, prognostication, and treatment for patients with these conditions.
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DOI：
10.1084/jem.20201268
发表时间：
2021-02-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dagher T;Maslah N;Edmond V;Cassinat B;Vainchenker W;Giraudier S;Pasquier F;Verger E;Niwa-Kawakita M;Lallemand-Breitenbach V;Plo I;Kiladjian JJ;Villeval JL;de Thé H
通讯作者：
de Thé H
影响因子：
21.3
作者：
Decker M;Martinez-Morentin L;Wang G;Lee Y;Liu Q;Leslie J;Ding L
通讯作者：
Ding L
影响因子：
11.4
作者：
Brkic S;Stivala S;Santopolo A;Szybinski J;Jungius S;Passweg JR;Tsakiris D;Dirnhofer S;Hutter G;Leonards K;Lischer HEL;Dettmer MS;Neel BG;Levine RL;Meyer SC
通讯作者：
Meyer SC
影响因子：
28.2
作者：
Elf S;Abdelfattah NS;Chen E;Perales-Patón J;Rosen EA;Ko A;Peisker F;Florescu N;Giannini S;Wolach O;Morgan EA;Tothova Z;Losman JA;Schneider RK;Al-Shahrour F;Mullally A
通讯作者：
Mullally A
影响因子：
20.3
作者：
Chang, Yunchao;Min, Jaeki;Mullighan, Charles G.
通讯作者：
Mullighan, Charles G.