Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis
Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis
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DOI：
10.1016/j.ccr.2005.03.023
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发表时间：
2005-04-01
期刊：
影响因子：
50.3
通讯作者：
Gilliland, DG
中科院分区：
文献类型：
--
作者：
Levine, RL;Wadleigh, M;Gilliland, DG
真性红细胞增多症（PV）、原发性血小板增多症（ET）和伴有骨髓纤维化的骨髓化生（MMM）是源自造血祖细胞的克隆性疾病。一种基于互联网的方案被用于从这些疾病的患者中收集临床信息和生物样本。高通量DNA重测序在164例PV患者中的121例粒细胞DNA样本中鉴定出一种反复出现的体细胞错义突变JAK2V617F，其中41例为纯合突变，80例为杂合突变。分子和细胞遗传学分析表明，纯合突变是由于突变等位基因的重复。在115例ET患者中的37例和46例MMM患者中的16例粒细胞DNA样本中也鉴定出JAK2V617F，但在269名正常个体中未观察到。体外分析表明，JAK2V617F是一种组成性激活的酪氨酸激酶。
Polycythemia vera (PV), essential thrombocythemia (ET), and myeloid metaplasia with myelofibrosis (MMM) are clonal disorders arising from hematopoietic progenitors. An internet-based protocol was used to collect clinical information and biological specimens from patients with these diseases. High-throughput DNA resequencing identified a recurrent somatic missense mutation JAK2V617F in granulocyte DNA samples of 121 of 164 PV patients, of which 41 had homozygous and 80 had heterozygous mutations. Molecular and cytogenetic analyses demonstrated that homozygous mutations were due to duplication of the mutant allele. JAK2V617F was also identified in granulocyte DNA samples from 37 of 115 ET and 16 of 46 MMM patients, but was not observed in 269 normal individuals. In vitro analysis demonstrated that JAK2V617F is a constitutively active tyrosine kinase.