Hematology and Medical Oncology, University of Utah, Salt Lake City, Utah, USA.
Curr Opin Hematol. 2010 Mar;17(2):110-6. doi: 10.1097/MOH.0b013e3283366b91.
The pathophysiology of Philadelphia-chromosome negative myeloproliferative disorders has significantly advanced with the discovery of JAK2V617F. The prevalence of JAK2V617F mutation has made it a much anticipated target for inhibition; this review will update and assess progress.
Many agents have been studied in preclinical trials, of which few have entered clinical trials. Data from the clinical trials are limited and mostly in the form of abstracts and reviews.
The prevalence of the JAK2V617F mutation in the classic Philadelphia-chromosome negative myeloproliferative disorders has made it a much anticipated target for inhibition. Present in greater than 90% of patients with polycythemia vera and approximately 50% of patients with essential thrombocythemia and primary myelofibrosis, it has been hoped that targeted inhibition of JAK2V617F would achieve similar disease control as imatinib mesylate has produced in chronic myeloid leukemia. However, JAK2V617F in the Philadelphia-chromosome negative myeloproliferative disorders, unlike bcr/abl tyrosine kinase in chronic myeloid leukemia, is not a causative but rather a secondary somatic mutation. As the JAK2 inhibitors move into phase III clinical trials, their efficacy and role in therapy is becoming clearer; however, there are still many questions needing answers.
随着 JAK2V617F 的发现，费城染色体阴性骨髓增殖性疾病的病理生理学有了显著进展。JAK2V617F 突变的流行使其成为抑制的预期靶点；这篇综述将更新并评估进展情况。
许多药物已在临床前试验中进行了研究，其中少数已进入临床试验。临床试验数据有限，且主要以摘要和综述的形式呈现。
经典费城染色体阴性骨髓增殖性疾病中 JAK2V617F 突变的流行使其成为抑制的预期靶点。该突变存在于超过 90%的真性红细胞增多症患者和约 50%的原发性血小板增多症和原发性骨髓纤维化患者中，人们曾希望靶向抑制 JAK2V617F 能够像伊马替尼治疗慢性髓性白血病那样实现类似的疾病控制。然而，与慢性髓性白血病中的 bcr/abl 酪氨酸激酶不同，费城染色体阴性骨髓增殖性疾病中的 JAK2V617F 不是病因性突变，而是继发性体细胞突变。随着 JAK2 抑制剂进入 III 期临床试验，其疗效和治疗作用变得更加清晰；然而，仍有许多问题需要解答。
