Andrikovics Hajnalka, Szilvási Anikó, Meggyesi Nóra, Király Viktória, Halm Gabriella, Lueff Sándor, Nahajevszky Sarolta, Mikala Gábor, Sipos Andrea, Lovas Nóra, Csukly Zoltán, Mátrai Zoltán, Tamáska Júlia, Tordai Attila, Masszi Tamás
Országos Gyógyintézeti Központ, Molekuláris Diagnosztikai Osztály, Budapest, Hungary.
Orv Hetil. 2007 Feb 4;148(5):203-10. doi: 10.1556/OH.2007.27860.
The Val617Phe point mutation of Janus kinase 2 gene is believed to participate in the pathogenesis of myeloproliferative syndrome characterised by the clonal alteration of hematopoietic stem cells. According to current results, the frequency of Val617Phe activating mutation is around 80% in polycythaemia vera, 35% in essential thrombocythemia, and 50% in chronic idiopathic myelofibrosis. The diagnoses of polycythemia vera, essential thrombocythemia and idiopathic myelofibrosis were so far based on the exclusion of secondary factors as well as bone marrow biopsy histology. The goal of the present work was to establish simple molecular genetic techniques for the routine testing of Janus kinase 2 gene Val617Phe mutation, and to compare the clinical phenotypes of Val617Phe mutation positive and negative myeloproliferative syndromes. We employed the allele specific polymerase chain technique for detection of Val617Phe mutation in 252 patients with myeloproliferative syndrome. We measured Val617Phe frequency as 85,4% (117/137) in polycythemia vera, 56,6% (56/99) in essential thrombocythemia, and 87,5% (14/16) in idiopathic myelofibrosis. We found significantly elevated hemoglobin levels and white blood cell counts (measured at the time of diagnosis) in Val617Phe-positive polycythemia vera and essential thrombocythemia patient groups compared to Val617Phe-negative patients. However, the frequencies of splenomegaly and other complications (thrombosis, bleeding, transformation to acute leukemia) were not significantly different between the mutation-positive and negative groups. In conclusion, the non-invasive mutation analysis of the Janus kinase 2 Val617Phe is suitable for routine laboratory application and helps the differential diagnosis of myeloproliferative syndrome. Although the exact role of Val617Phe mutation testing has not yet been identified on the basis of a broad professional consensus, the testing is suggested in cases of erythrocytoses and thrombocytoses of unknown origin.
Janus激酶2基因的Val617Phe点突变被认为参与了以造血干细胞克隆性改变为特征的骨髓增殖综合征的发病机制。根据目前的结果，Val617Phe激活突变的频率在真性红细胞增多症中约为80%，在原发性血小板增多症中为35%，在慢性特发性骨髓纤维化中为50%。迄今为止，真性红细胞增多症、原发性血小板增多症和特发性骨髓纤维化的诊断基于排除继发因素以及骨髓活检组织学检查。本研究的目的是建立用于常规检测Janus激酶2基因Val617Phe突变的简单分子遗传学技术，并比较Val617Phe突变阳性和阴性骨髓增殖综合征的临床表型。我们采用等位基因特异性聚合酶链技术检测252例骨髓增殖综合征患者的Val617Phe突变。我们测得真性红细胞增多症中Val617Phe频率为85.4%（117/137），原发性血小板增多症中为56.6%（56/99），特发性骨髓纤维化中为87.5%（14/16）。我们发现，与Val617Phe阴性患者相比，Val617Phe阳性的真性红细胞增多症和原发性血小板增多症患者组的血红蛋白水平和白细胞计数（诊断时测量）显著升高。然而，突变阳性和阴性组之间脾肿大和其他并发症（血栓形成、出血、转化为急性白血病）的发生率没有显著差异。总之，Janus激酶2 Val617Phe的非侵入性突变分析适用于常规实验室应用，并有助于骨髓增殖综合征的鉴别诊断。尽管基于广泛的专业共识尚未确定Val617Phe突变检测的确切作用，但对于不明原因的红细胞增多症和血小板增多症病例建议进行该检测。
