Hobbs Gabriela S, Rozelle Sarah, Mullally Ann
Division of Hematology/Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA.
Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Hematol Oncol Clin North Am. 2017 Aug;31(4):613-626. doi: 10.1016/j.hoc.2017.04.002. Epub 2017 May 17.
Following the discovery of the JAK2V617F mutation, Janus kinase (JAK) 2 inhibitors were developed as rationally designed therapy in myeloproliferative neoplasms (MPNs). Although JAK2 inhibitors have clinical efficacy in MPN, they are not clonally selective for the JAK2V617F-mutant cells. Because activated JAK-signal transducer and activator of transcription (STAT) signaling is a common feature of MPN, JAK2 inhibitors are efficacious regardless of the specific MPN phenotypic driver mutation. The Food and Drug Administration approved the JAK1/JAK2 inhibitor, ruxolitinib, for the treatment of myelofibrosis and polycythemia vera. Additional JAK2 inhibitors are currently in advanced phased clinical trials.
在发现JAK2V617F突变后，开发了Janus激酶（JAK）2抑制剂作为骨髓增殖性肿瘤（MPN）的合理设计疗法。尽管JAK2抑制剂在MPN中具有临床疗效，但它们对JAK2V617F突变细胞不具有克隆选择性。由于激活的JAK-信号转导子和转录激活子（STAT）信号传导是MPN的共同特征，因此无论特定的MPN表型驱动突变如何，JAK2抑制剂均有效。美国食品药品监督管理局批准了JAK1/JAK2抑制剂芦可替尼用于治疗骨髓纤维化和真性红细胞增多症。其他JAK2抑制剂目前正处于晚期临床试验阶段。
