O'Sullivan Jennifer M, Harrison Claire N
Department of Haematology, Guy's and St Thomas' NHS Foundation Trust, London, UK. Electronic address: jennifer.o'
Department of Haematology, Guy's and St Thomas' NHS Foundation Trust, London, UK.
Mol Cell Endocrinol. 2017 Aug 15;451:71-79. doi: 10.1016/j.mce.2017.01.050. Epub 2017 Feb 3.
Myeloproliferative neoplasms (MPN) are a group of disorders defined by clonal proliferation of mature myeloid cells with overlapping clinical features. The driver mutations of these disorders, namely JAK2 (Janus Kinase), MPL (Myeloproliferative Leukaemia Virus) and CALR (Calreticulin) upregulate JAK-STAT signaling with increase in downstream transcription and gene expression. Epigenetic mutations are prevalent in MPNs but their interplay with aberrant JAK-STAT signaling is not known. This understanding lead to development of first targeted treatment in MPN; ruxolitinib for primary myelofibrosis. This has shown clinical benefit in overall survival and symptoms improvement but has yet to show significant disease modifying effects. This review will focus on contemporaneous understanding of altered JAK-STAT signaling in MPN and targeted treatments in clinical practice.
骨髓增殖性肿瘤（MPN）是一组由成熟髓系细胞克隆性增殖定义的疾病，具有重叠的临床特征。这些疾病的驱动突变，即JAK2（Janus激酶）、MPL（骨髓增殖性白血病病毒）和CALR（钙网蛋白），上调JAK-STAT信号传导，增加下游转录和基因表达。表观遗传突变在MPN中普遍存在，但其与异常JAK-STAT信号传导的相互作用尚不清楚。这种认识促成了MPN首个靶向治疗药物的开发；用于原发性骨髓纤维化的鲁索替尼。它已显示出对总体生存和症状改善的临床益处，但尚未显示出显著的疾病修饰作用。本综述将聚焦于对MPN中JAK-STAT信号改变的当代理解以及临床实践中的靶向治疗。
