Krähling Tünde, Balassa Katalin, Meggyesi Nóra, Bors András, Csomor Judit, Bátai Árpád, Halm Gabriella, Egyed Miklós, Fekete Sándor, Reményi Péter, Masszi Tamás, Tordai Attila, Andrikovics Hajnalka
Országos Vérellátó Szolgálat Molekuláris Diagnosztikai Laboratórium Budapest Karolina út 19-21. 1113.
Egyesített Szent István és Szent László Kórház Hematológiai és Őssejt-transzplantációs Osztály Budapest.
Orv Hetil. 2014 Dec 28;155(52):2074-81. doi: 10.1556/OH.2014.30051.
Mutations in Janus kinase 2, calreticulin and thrombopoietin receptor genes have been identified in the genetic background of Philadelphia chromosome negative, "classic" myeloproliferative neoplasms.
The aim of the authors was to identify driver mutations in a large myeloproliferative cohort of 949 patients.
A complex array of molecular techniques (qualitative and quantitative allele-specific polymerase chain reactions, fragment analyzes, high resolution melting and Sanger sequencing) was applied.
All 354 patients with polycythemia vera carried Janus kinase 2 mutations (V617F 98.6%, exon 12: 1.4%). In essential thrombocythemia (n = 468), the frequency of V617F was 61.3% (n = 287), that of calreticulin 25.2% (n = 118), and that of thrombopoietin receptor mutations 2.1% (n = 10), while 11.3% (n = 53) were triple-negative. Similar distribution was observed in primary myelofibrosis (n = 127): 58.3% (n = 74) V617F, 23.6% (n = 30) calreticulin, 6.3% (n = 8) thrombopoietin receptor mutation positive and 11.8% (n = 15) triple-negative.
The recent discovery of calreticulin gene mutations led to definite molecular diagnostics in around 90% of clonal myeloproliferative cases.
在费城染色体阴性的“经典”骨髓增殖性肿瘤的遗传背景中，已鉴定出Janus激酶2、钙网蛋白和血小板生成素受体基因的突变。
作者的目的是在949例患者的大型骨髓增殖性队列中鉴定驱动突变。
应用了一系列复杂的分子技术（定性和定量等位基因特异性聚合酶链反应、片段分析、高分辨率熔解和桑格测序）。
所有354例真性红细胞增多症患者均携带Janus激酶2突变（V617F 98.6%，第12外显子：1.4%）。在原发性血小板增多症（n = 468）中，V617F的频率为61.3%（n = 287），钙网蛋白为25.2%（n = 118），血小板生成素受体突变为2.1%（n = 10），而11.3%（n = 53）为三阴性。在原发性骨髓纤维化（n = 127）中观察到类似的分布：58.3%（n = 74）为V617F，23.6%（n = 30）为钙网蛋白，6.3%（n = 8）血小板生成素受体突变阳性，11.8%（n = 15）为三阴性。
钙网蛋白基因突变的最新发现导致约90%的克隆性骨髓增殖性病例得到明确的分子诊断。
