Polycythemia vera. II. Hypersensitivity of bone marrow erythroid, granulocyte-macrophage, and megakaryocyte progenitor cells to interleukin-3 and granulocyte-macrophage colony-stimulating factor.
Polycythemia vera. II. Hypersensitivity of bone marrow erythroid, granulocyte-macrophage, and megakaryocyte progenitor cells to interleukin-3 and granulocyte-macrophage colony-stimulating factor.
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DOI：
10.1182/blood.v80.4.891.891
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发表时间：
1992
期刊：
影响因子：
20.3
通讯作者：
C. Dai;S. Krantz;EN Dessypris;RT Jr Means;S. Horn;H. Gilbert
中科院分区：
文献类型：
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作者：
C. Dai;S. Krantz;EN Dessypris;RT Jr Means;S. Horn;H. Gilbert
真性红细胞增多症(PV)是一种以骨髓红系、粒系和巨核系细胞增多为特征的造血干细胞克隆性疾病。我们以前报道过高纯度的PV红系(BFU-E)对重组人白介素3(rIL-3)具有超敏反应。由于这些细胞可能只是一个亚群，并不代表骨髓祖细胞，我们现在已经研究了部分纯化的骨髓造血祖细胞。与正常骨髓BFU-E相比，PV骨髓BFU-E对rIL-3的敏感性增加38倍，对重组人促红细胞生成素(REPO)的敏感性增加4.3倍。此外，PV骨髓集落形成单位粒-巨噬细胞(CFU-GM)和CFU-巨核细胞(CFU-MK)对rIL-3和人重组粒细胞-巨噬细胞集落刺激因子(RGM-CSF)也表现出明显的超敏反应。RGM-CSF和血BFU-E的剂量-反应曲线显示敏感性增加了48倍。RIL-4、rIL-6、人重组粒细胞集落刺激因子(rg-CSF)、巨噬细胞集落刺激因子(rm-CSF)对正常BFU-E无明显作用，PV细胞条件培养液对正常BFU-E也无明显影响。125I-REPO放射自显影显示PV BFU-E与CFU-E成熟后EPO受体增加，与正常BFU-E相似，但与正常CD34+细胞相比，PV CD34+细胞对125I-rIL-3的特异性结合没有增加。这些研究表明，PV骨髓造血祖细胞对rIL-3和RGM-CSF高度敏感，与PV血液中的BFU-E相似。虽然其机制不是由于增强了rIL-3的结合，但PV祖细胞对IL-3和GM-CSF的超敏反应可能是PV发病的关键因素。
Polycythemia vera (PV) is a clonal disease of the hematopoietic stem cell characterized by a hyperplasia of marrow erythropoiesis, granulocytopoiesis, and megakaryocytopoiesis. We previously reported that highly purified PV blood burst-forming units-erythroid (BFU-E) are hypersensitive to recombinant human interleukin-3 (rIL-3). Because these cells may be only a subset, and not representative of marrow progenitors, we have now studied partially purified marrow hematopoietic progenitor cells. Dose-response experiments with PV marrow BFU-E showed a 38-fold increase in sensitivity to rIL-3 and a 4.3-fold increase in sensitivity to recombinant human erythropoietin (rEpo) compared with normal marrow BFU-E. In addition, PV marrow colony-forming units-granulocyte-macrophage (CFU-GM) and CFU-megakaryocyte (CFU-MK) also showed a marked hypersensitivity to rIL-3 and to human recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF). Dose-response curves with rGM-CSF and blood BFU-E showed a 48-fold increase in sensitivity. No effect of rIL-4, rIL-6, human recombinant granulocyte-CSF (rG-CSF), or macrophage-CSF (rM-CSF) was evident, nor was there any effect of PV cell-conditioned medium on normal BFU-E, when compared with normal cell-conditioned medium. Autoradiography with 125I-rEpo showed an increase in Epo receptors after maturation of PV BFU-E to CFU-E similar to that shown with normal BFU-E, but no increase of specific binding of 125I-rIL-3 by PV CD34+ cells was seen compared with normal CD34+ cells. These studies show that PV marrow hematopoietic progenitor cells are hypersensitive to rIL-3 and rGM-CSF, similar to PV blood BFU-E. While the mechanism does not appear to be due to enhanced binding of rIL-3, the hypersensitivity of PV progenitor cells to IL-3 and GM-CSF may be a key factor in the pathogenesis of PV.