Rozovski Uri, Verstovsek Srdan, Manshouri Taghi, Dembitz Vilma, Bozinovic Ksenija, Newberry Kate, Zhang Ying, Bove Joseph E, Pierce Sherry, Kantarjian Hagop, Estrov Zeev
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Davidoff Medical Center, Beilinson Hospital, Petah Tikva, Israel.
Haematologica. 2017 Jan;102(1):79-84. doi: 10.3324/haematol.2016.149765. Epub 2016 Sep 29.
In most patients with primary myelofibrosis, one of three mutually exclusive somatic mutations is detected. In approximately 60% of patients, the Janus kinase 2 gene is mutated, in 20%, the calreticulin gene is mutated, and in 5%, the myeloproliferative leukemia virus gene is mutated. Although patients with mutated calreticulin or myeloproliferative leukemia genes have a favorable outcome, and those with none of these mutations have an unfavorable outcome, prognostication based on mutation status is challenging due to the heterogeneous survival of patients with mutated Janus kinase 2. To develop a prognostic model based on mutation status, we screened primary myelofibrosis patients seen at the MD Anderson Cancer Center, Houston, USA, between 2000 and 2013 for the presence of Janus kinase 2, calreticulin, and myeloproliferative leukemia mutations. Of 344 primary myelofibrosis patients, Janus kinase 2 was detected in 226 (66%), calreticulin mutation in 43 (12%), and myeloproliferative leukemia mutation in 16 (5%); 59 patients (17%) were triple-negatives. A 50% cut-off dichotomized Janus kinase 2-mutated patients into those with high Janus kinase 2 allele burden and favorable survival and those with low Janus kinase 2 allele burden and unfavorable survival. Patients with a favorable mutation status (high Janus kinase 2 allele burden/myeloproliferative leukemia/calreticulin mutation) and aged 65 years or under had a median survival of 126 months. Patients with one risk factor (low Janus kinase 2 allele burden/triple-negative or age >65 years) had an intermediate survival duration, and patients aged over 65 years with an adverse mutation status (low Janus kinase 2 allele burden or triple-negative) had a median survival of only 35 months. Our simple and easily applied age- and mutation status-based scoring system accurately predicted the survival of patients with primary myelofibrosis.
在大多数原发性骨髓纤维化患者中，可检测到三种相互排斥的体细胞突变之一。在大约60%的患者中，Janus激酶2基因发生突变；20%的患者中，钙网蛋白基因发生突变；5%的患者中，骨髓增殖性白血病病毒基因发生突变。尽管钙网蛋白或骨髓增殖性白血病基因突变的患者预后良好，而无这些突变的患者预后不良，但由于Janus激酶2基因突变患者的生存情况存在异质性，基于突变状态进行预后评估具有挑战性。为了开发一种基于突变状态的预后模型，我们对2000年至2013年期间在美国休斯敦MD安德森癌症中心就诊的原发性骨髓纤维化患者进行筛查，以检测是否存在Janus激酶2、钙网蛋白和骨髓增殖性白血病突变。在344例原发性骨髓纤维化患者中，226例（66%）检测到Janus激酶2突变，43例（12%）检测到钙网蛋白突变，16例（5%）检测到骨髓增殖性白血病突变；59例患者（17%）为三阴性。以50%为界值，将Janus激酶2突变患者分为Janus激酶2等位基因负担高且生存良好的患者和Janus激酶2等位基因负担低且生存不良的患者。具有良好突变状态（Janus激酶2等位基因负担高/骨髓增殖性白血病/钙网蛋白突变）且年龄在65岁及以下的患者中位生存期为126个月。具有一个危险因素（Janus激酶2等位基因负担低/三阴性或年龄>65岁）的患者生存时间中等，而年龄超过65岁且具有不良突变状态（Janus激酶2等位基因负担低或三阴性）的患者中位生存期仅为35个月。我们基于年龄和突变状态的简单易用的评分系统准确预测了原发性骨髓纤维化患者的生存情况。
