JAK2突变体（例如，JAK2V617F）及其作为骨髓增殖性肿瘤药物靶点的重要性。
JAK2 mutants (e.g., JAK2V617F) and their importance as drug targets in myeloproliferative neoplasms.
作者信息
Gäbler Karoline, Behrmann Iris, Haan Claude
机构信息
Signal Transduction Laboratory; Life Sciences Research Unit; University of Luxembourg; Luxembourg.
出版信息
JAKSTAT. 2013 Jul 1;2(3):e25025. doi: 10.4161/jkst.25025. Epub 2013 May 14.
Abstract
The Janus kinase 2 (JAK2) mutant V617F and other JAK mutants are found in patients with myeloproliferative neoplasms and leukemias. Due to their involvement in neoplasia and inflammatory disorders, Janus kinases are promising targets for kinase inhibitor therapy. Several small-molecule compounds are evaluated in clinical trials for myelofibrosis, and ruxolitinib (INCB018424, Jakafi®) was the first Janus kinase inhibitor to receive clinical approval. In this review we provide an overview of JAK2V617F signaling and its inhibition by small-molecule kinase inhibitors. In addition, myeloproliferative neoplasms are discussed regarding the role of JAK2V617F and other mutant proteins of possible relevance. We further give an overview about treatment options with special emphasis on possible combination therapies.
摘要
在骨髓增殖性肿瘤和白血病患者中发现了Janus激酶2（JAK2）突变体V617F及其他JAK突变体。由于Janus激酶参与肿瘤形成和炎症性疾病，它们是激酶抑制剂治疗的有前景的靶点。几种小分子化合物正在进行骨髓纤维化的临床试验评估，而鲁索替尼（INCB018424，Jakafi®）是首个获得临床批准的Janus激酶抑制剂。在本综述中，我们概述了JAK2V617F信号传导及其被小分子激酶抑制剂抑制的情况。此外，还讨论了骨髓增殖性肿瘤中JAK2V617F及其他可能相关突变蛋白的作用。我们还特别强调可能的联合治疗，对治疗选择进行了概述。
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