Morgan Kelly J, Gilliland D Gary
Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Annu Rev Med. 2008;59:213-22. doi: 10.1146/annurev.med.59.061506.154159.
Myeloproliferative disorders (MPDs) are characterized by a clonal expansion of myeloid cells. Over the past two years, the identification of the JAK2V617F mutation in most cases of polycythemia vera (PV) as well as approximately 50% of patients with essential thrombocythemia (ET) and idiopathic myelofibrosis (IMF) has greatly advanced our understanding of MPDs. The JAK2V617F mutation alters the JAK2 tyrosine kinase to confer constitutive activation and affect downstream signaling pathways. Data from mouse models demonstrate that the mutation is sufficient for development of PV, but additional work is needed to better understand how this allele functions in ET and IMF. Regardless of the various pathologies, the JAK2V617F discovery highlights the importance of JAK-STAT signaling in myeloid differentiation and focuses effort on developing a clinically relevant JAK2 inhibitor.
骨髓增殖性疾病（MPDs）的特征是髓系细胞的克隆性扩增。在过去两年中，大多数真性红细胞增多症（PV）病例以及约50%的原发性血小板增多症（ET）和原发性骨髓纤维化（IMF）患者中JAK2V617F突变的发现，极大地推动了我们对MPDs的认识。JAK2V617F突变改变了JAK2酪氨酸激酶，使其具有组成性激活并影响下游信号通路。来自小鼠模型的数据表明，该突变足以导致PV的发生，但还需要更多研究来更好地了解该等位基因在ET和IMF中的作用机制。无论存在何种病理情况，JAK2V617F的发现都凸显了JAK-STAT信号在髓系分化中的重要性，并促使人们致力于开发具有临床相关性的JAK2抑制剂。
