Oppliger Leibundgut Elisabeth, Horn Michael Peter, Brunold Claudio, Pfanner-Meyer Brigitte, Marti Dorothee, Hirsiger Hans, Tobler Andreas, Zwicky Caroline
Hematology Department, University Hospital, CH-3010 Berne, Switzerland.
Haematologica. 2006 Nov;91(11):1465-72.
The presence of circulating hematopoietic progenitor cells in patients with myeloproliferative diseases (MPD) has been described. However, the exact nature of such progenitor cells has not been specified until now. The aim of this work was to investigate the presence of endothelial precursor cells in the blood of patients with MPD and to assess the role of the endothelial cell lineage in the pathophysiology of this disease.
Endothelial progenitor cell marker expression (CD34, prominin (CD133), kinase insert domain receptor (KDR) or vascular endothelial growth factor receptor 2 (VEGFR2), and von Willebrand factor) was assessed in the blood of 53 patients with MPD by quantitative polymerase chain reaction. Clonogenic stem cell assays were performed with progenitor cells and monocytes to assess differentiation towards the endothelial cell lineage. The patients' were divided according to whether they had essential thrombocythemia (ET, n=17), polycythemia vera (PV, n=21) or chronic idiopathic myelofibrosis (CIMF, n=15) and their data compared with data from normal controls (n=16) and patients with secondary thrombo- or erythrocytosis (n=17).
Trafficking of CD34-positive cells was increased above the physiological level in 4/17 patients with ET, 5/21 patients with PV and 13/15 patients with CIMF. A subset of patients with CIMF co-expressed the markers CD34, prominin (CD133) and KDR, suggesting the presence of endothelial precursors among the circulating progenitor cells. Clonogenic stem cell assays confirmed differentiation towards both the hematopoietic and the endothelial cell lineage in 5/10 patients with CIMF. Furthermore, the molecular markers trisomy 8 and JAK2 V617F were found in the grown endothelial cells of patients positive for trisomy 8 or JAK2 V617F in the peripheral blood, confirming the common clonal origin of both hematopoietic and endothelial cell lineages.
Endothelial precursor cells are increased in the blood of a subset of patients with CIMF, and peripheral endothelial cells bear the same molecular markers as hematopoietic cells, suggesting a primary role of pathological endothelial cells in this disease.
骨髓增殖性疾病（MPD）患者体内存在循环造血祖细胞已有相关描述。然而，迄今为止，此类祖细胞的确切性质尚未明确。本研究旨在调查MPD患者血液中内皮祖细胞的存在情况，并评估内皮细胞谱系在该疾病病理生理学中的作用。
采用定量聚合酶链反应评估53例MPD患者血液中内皮祖细胞标志物（CD34、prominin（CD133）、激酶插入结构域受体（KDR）或血管内皮生长因子受体2（VEGFR2）以及血管性血友病因子）的表达。对祖细胞和单核细胞进行集落形成干细胞检测，以评估向内皮细胞谱系的分化情况。根据患者是否患有原发性血小板增多症（ET，n = 17）、真性红细胞增多症（PV，n = 21）或慢性特发性骨髓纤维化（CIMF，n = 15）进行分组，并将他们的数据与正常对照组（n = 16）和继发性血栓形成或红细胞增多症患者（n = 17）的数据进行比较。
17例ET患者中有4例、21例PV患者中有5例以及15例CIMF患者中有13例的CD34阳性细胞运输量高于生理水平。一部分CIMF患者共表达CD34、prominin（CD133）和KDR标志物，提示循环祖细胞中存在内皮祖细胞。集落形成干细胞检测证实10例CIMF患者中有5例可向内皮细胞谱系和造血细胞谱系分化。此外，在8号染色体三体或外周血JAK2 V617F阳性患者培养的内皮细胞中发现了8号染色体三体和JAK2 V617F分子标志物，证实造血细胞谱系和内皮细胞谱系具有共同的克隆起源。
一部分CIMF患者血液中的内皮祖细胞数量增加，外周内皮细胞与造血细胞具有相同的分子标志物，提示病理性内皮细胞在该疾病中起主要作用。
