Impaired expression of the thrombopoietin receptor by platelets from patients with polycythemia vera
Impaired expression of the thrombopoietin receptor by platelets from patients with polycythemia vera
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DOI：
10.1056/nejm199802263380903
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发表时间：
1998-02-26
影响因子：
158.5
通讯作者：
Spivak, JL
中科院分区：
文献类型：
--
作者：
Moliterno, AR;Hankins, WD;Spivak, JL
背景真性红细胞增多症起源于多能造血祖细胞，其病因尚不清楚，血小板生成素是一种造血生长因子，调节多能造血祖细胞和血小板的产生。为了探讨血小板生成素介导的信号转导异常可能参与真性红细胞增多症的发病机制，我们检测了真性红细胞增多症患者血小板中血小板生成素诱导的蛋白酪氨酸磷酸化和血小板生成素受体的表达。方法从真性红细胞增多症或其他慢性骨髓增生性疾病患者和对照组的血液中分离血小板，用血小板生成素或凝血酶作用于血小板，然后用免疫印迹法检测血小板蛋白酪氨酸磷酸化和蛋白表达。结果真性红细胞增多症20例，特发性骨髓纤维化3例，血小板生成素介导的蛋白酪氨酸磷酸化水平受损，而原发性血小板增多症4例，慢性粒细胞白血病3例，继发性红细胞增多症6例，缺铁性贫血2例，血色沉着4例，正常对照组5例均未见异常。在真性红细胞增多症患者的血小板中，凝血酶介导的酪氨酸蛋白磷酸化是完整的，参与这一过程的酪氨酸激酶和底物存在于正常数量。34例真性红细胞增多症患者中34例和14例特发性骨髓纤维化患者中13例血小板生成素受体MPL表达明显减少或缺失。在这两种疾病的患者中，血小板生成素诱导的蛋白质酪氨酸磷酸化受损与MPL表达显著降低或缺乏一致相关。在真性红细胞增多症患者中，血小板表达MPL减少与巨核细胞表达MPL减少有关。结论血小板生成素受体MPL表达降低是真性红细胞增多症和特发性骨髓纤维化的特征，这种异常可能是真性红细胞增多症与其他形式的红细胞增多症的区别。(C)1998年，马萨诸塞州医学会。
Background The cause of polycythemia vera, which originates from a multipotent hematopoietic progenitor cell, is unknown, Thrombopoietin is a hematopoietic growth factor that regulates the production of multipotent hematopoietic progenitor cells and platelets. To evaluate the possibility that an abnormality in thrombopoietin-mediated signal transduction might be involved in the pathogenesis of polycythemia vera, we examined thrombopoietin-induced tyrosine phosphorylation of proteins and the expression of the thrombopoietin receptor in platelets from patients with the disease.Methods Platelets were isolated from the blood of patients with polycythemia vera or other chronic myeloproliferative disorders and control subjects, The platelets were exposed to either thrombopoietin or thrombin and then lysed for analysis of tyrosine phosphorylation of platelet proteins and the expression of the proteins by means of immunoblotting, Expression of the thrombopoietin receptor (Mpl) by platelets and megakaryocytes was also assessed.Results Thrombopoietin-mediated tyrosine phosphorylation of proteins was impaired in platelets from 20 patients with polycythemia vera and 3 with idiopathic myelofibrosis, but not in 4 patients with essential thrombocytosis, 3 with chronic myelogenous leukemia, 6 with secondary erythrocytosis, 2 with iron-deficiency anemia, 4 with hemochromatosis, or 5 normal subjects. Thrombin-mediated tyrosine phosphorylation of proteins was intact in platelets from patients with polycythemia vera, and the tyrosine kinases and substrates involved in the process were present in normal amounts. However, expression of the platelet thrombopoietin receptor Mpl was markedly reduced or absent in 34 of 34 patients with polycythemia vera and in 13 of 14 patients with idiopathic myelofibrosis. Impaired thrombopoietin-induced tyrosine phosphorylation of proteins in patients with these two diseases was uniformly associated with markedly reduced expression of Mpl or the lack of its expression. In patients with polycythemia vera, reduced expression of Mpl by platelets was associated with reduced expression of Mpl by megakaryocytes.Conclusions Reduced expression of the thrombopoietin receptor Mpl is characteristic of polycythemia vera and idiopathic myelofibrosis, The abnormality appears to distinguish polycythemia vera from other forms of erythrocytosis. (C) 1998, Massachusetts Medical Society.