Schafer Andrew I
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Blood. 2006 Jun 1;107(11):4214-22. doi: 10.1182/blood-2005-08-3526. Epub 2006 Feb 16.
Recent insights into the molecular mechanisms of polycythemia vera (PV) and essential thrombocythemia (ET) are challenging the traditional diagnostic classification of these myeloproliferative disorders (MPDs). Clonality analysis using X-chromosome inactivation patterns has revealed apparent heterogeneity among the MPDs. The recently discovered single somatic activating point mutation in the JAK2 gene (JAK2-V617F) is found in the great majority of patients with PV, but also in many patients with phenotypically classified ET and other MPDs. In contrast to the acquired MPDs, mutations of the erythropoietin receptor and thrombopoietin receptor have been identified in familial forms of nonclonal erythrocytosis and thrombocytosis, respectively. The mechanisms of major clinical complications of PV and ET remain poorly understood. Quantitative or qualitative abnormalities of red cells and platelets do not provide clear explanations for the thrombotic and bleeding tendency in these MPDs, suggesting the need for entirely new lines of research in this area. Recently reported randomized clinical trials have demonstrated the efficacy and safety of low-dose aspirin in PV, and an excess rate of arterial thrombosis, major bleeding, and myelofibrotic transformation, but decreased venous thrombosis, in patients with ET treated with anagrelide plus aspirin compared to hydroxyurea plus aspirin.
近期对真性红细胞增多症（PV）和原发性血小板增多症（ET）分子机制的深入了解正在挑战这些骨髓增殖性疾病（MPD）的传统诊断分类。利用X染色体失活模式进行的克隆性分析揭示了MPD之间明显的异质性。最近在绝大多数PV患者中发现了JAK2基因中的单个体细胞激活点突变（JAK2-V617F），但在许多表型分类为ET的患者和其他MPD患者中也有发现。与获得性MPD不同，在家族性非克隆性红细胞增多症和血小板增多症中分别鉴定出促红细胞生成素受体和血小板生成素受体的突变。PV和ET主要临床并发症的机制仍知之甚少。红细胞和血小板的定量或定性异常并不能为这些MPD的血栓形成和出血倾向提供明确解释，这表明该领域需要全新的研究方向。最近报道的随机临床试验证明了低剂量阿司匹林在PV中的疗效和安全性，以及与羟基脲加阿司匹林治疗的ET患者相比，使用阿那格雷加阿司匹林治疗的ET患者动脉血栓形成过多、大出血和骨髓纤维化转化发生率较高，但静脉血栓形成减少。
