Wadleigh Martha, Tefferi Ayalew
Leukemia Program, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Clin Adv Hematol Oncol. 2010 Aug;8(8):557-63.
The discovery of a common Janus kinase 2 (JAK2) point mutation, JAK2V617F, in myeloproliferative neoplasms has generated enormous interest in the development and therapeutic use of small molecule JAK2 inhibitor-targeted therapy in these diseases. A handful of compounds are currently in clinical development in primary myelofibrosis or post-polycythemia vera (PV)/essential thrombocythemia (ET) myelofibrosis. To date, clinical benefit has been demonstrated in terms of reduction of splenomegaly, improvement in constitutional symptoms, and control of leukocytosis. Some of the drugs have also been evaluated in PV and ET, with demonstrated activity against erythrocytosis, thrombocytosis, pruritus, and splenomegaly. However, drug effect on bone marrow fibrosis or JAK2 allele burden has been modest so far. Regardless, it is important to keep in mind that current anti-JAK2 treatment trials constitute only the beginning of many upcoming similar clinical trials, and that it is premature to make generalizations or any form of comparative conclusions regarding drug activity or toxicity.
在骨髓增殖性肿瘤中发现常见的Janus激酶2（JAK2）点突变JAK2V617F，引发了人们对小分子JAK2抑制剂靶向治疗在这些疾病中的开发和治疗应用的极大兴趣。目前有几种化合物正在原发性骨髓纤维化或真性红细胞增多症（PV）/原发性血小板增多症（ET）后骨髓纤维化的临床开发中。迄今为止，已在脾肿大缩小、全身症状改善和白细胞增多控制方面证明了临床益处。其中一些药物也已在PV和ET中进行评估，显示出对红细胞增多症、血小板增多症、瘙痒和脾肿大的活性。然而，到目前为止，药物对骨髓纤维化或JAK2等位基因负担的影响不大。无论如何，重要的是要记住，目前的抗JAK2治疗试验仅仅是许多即将开展的类似临床试验的开端，就药物活性或毒性进行概括或任何形式的比较结论都为时过早。
