Atallah Ehab, Verstovsek Srdan
Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Expert Rev Anticancer Ther. 2009 May;9(5):663-70. doi: 10.1586/era.09.14.
The discovery of the Janus kinase (JAK)2 V617F mutation in patients with myeloproliferative neoplasms was a major milestone in understanding the biology of those disorders. Several groups simultaneously reported on the high incidence of this mutation in patients with myeloproliferative neoplasms: almost all patients with polycythemia vera harbor the mutation and about 50% of patients with essential thrombocythemia and primary myelofibrosis have the mutation, making the development of JAK2 tyrosine kinase inhibitors an attractive therapeutic goal. In addition, inhibition of JAK2 kinase may have a therapeutic role in other hematologic malignancies, such as chronic myeloid leukemia or lymphoma. A number of molecules that inhibit JAK2 kinase have been described in the literature, and several are being evaluated in a clinical setting. Here, we summarize current clinical experience with JAK2 inhibitors.
骨髓增殖性肿瘤患者中Janus激酶(JAK)2 V617F突变的发现是理解这些疾病生物学特性的一个重要里程碑。多个研究小组同时报告了该突变在骨髓增殖性肿瘤患者中的高发生率:几乎所有真性红细胞增多症患者都携带该突变,约50%的原发性血小板增多症和原发性骨髓纤维化患者有此突变,这使得JAK2酪氨酸激酶抑制剂的研发成为一个有吸引力的治疗目标。此外,抑制JAK2激酶可能在其他血液系统恶性肿瘤,如慢性髓性白血病或淋巴瘤中发挥治疗作用。文献中已描述了多种抑制JAK2激酶的分子,其中几种正在临床环境中进行评估。在此,我们总结了JAK2抑制剂的当前临床经验。