Miyawaki Hiroshi, Kioka Hidetaka, Sato Kazuaki, Kurashige Masako, Ozawa Takayuki, Shibayama Hirohiko, Hikoso Shungo, Morii Eiichi, Yamauchi-Takihara Keiko, Sakata Yasushi
Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Japan.
Department of Pathology, Osaka University Graduate School of Medicine, Japan.
Intern Med. 2020 Jan 15;59(2):229-233. doi: 10.2169/internalmedicine.3528-19. Epub 2019 Sep 18.
Constitutive activation of the Janus kinase/signal transduction and activator of transcription (JAK-STAT) signaling pathway plays a central role in the pathogenesis of myelofibrosis (MF) and pulmonary hypertension (PH) is a known complication of MF. On the other hand, it has been proposed that the JAK-STAT pathway, especially signal transducer and activation of transcription (STAT) 3 activation, protects cardiomyocytes from various stresses. We describe the case of a patient with MF-associated PH who developed left ventricular dysfunction after five years of treatment with the JAK 1/2 inhibitor, ruxolitinib. This is the first report with histopathological findings that demonstrate possible contradictory effects of a JAK 1/2 inhibitor: improvement of MF-associated PH and cardiotoxicity.
Janus激酶/信号转导及转录激活因子（JAK-STAT）信号通路的组成性激活在骨髓纤维化（MF）的发病机制中起核心作用，而肺动脉高压（PH）是MF的一种已知并发症。另一方面，有人提出JAK-STAT通路，尤其是信号转导及转录激活因子（STAT）3的激活，可保护心肌细胞免受各种应激。我们描述了一例MF相关PH患者的病例，该患者在接受JAK 1/2抑制剂鲁索替尼治疗五年后出现左心室功能障碍。这是第一份有组织病理学发现的报告，证明了JAK 1/2抑制剂可能存在的矛盾作用：改善MF相关PH和心脏毒性。
