Croizat H, Amato D, McLeod D L, Eskinazi D, Axelrad A A
Blood. 1983 Sep;62(3):578-84.
We have studied the behavior in culture of circulating restricted hemopoietic progenitor cells from patients with idiopathic myelofibrosis (IMF), polycythemia vera (PV), and essential thrombocytopenia (ET). We have found differences in circulating granulocyte-macrophage, erythroid, and megakaryocytic progenitors that appear to be specific for these chronic myeloproliferative disorders. In IMF, most affected were granulocyte-macrophage progenitor cells (CFU-C), which circulated in increased numbers and were heterogeneous in their sensitivity to the regulatory factor(s) present in phytohemagglutinin (PHA) stimulated T-lymphocyte conditioned medium (CM). Most CFU-C were either highly sensitive to, or independent from, stimulatory factors, while others showed normal sensitivity. In some IMF patients, circulating megakaryocytic progenitors (CFU-M) were present that were capable of giving rise to colonies in the absence of added CM or erythropoietin (EPO). In PV, we confirmed the presence of circulating erythroid progenitor cells that give rise to colonies in culture without the addition of EPO. The number of circulating CFU-C was normal and they responded normally to CM. In ET, failure to detect 7-day circulating restricted progenitor cells was a common observation; the level of other circulating restricted progenitors was in the low normal range. Thus, despite certain common features, including a primary lesion at the level of the pluripotential hemopoietic stem cell, the myeloproliferative disorders differ with respect to the behavior in culture of their circulating restricted progenitor cells. These results have led us to postulate a second regulatory lesion in the pluripotential stem cell that differs in these disorders and is expressed at the level of the respective restricted progenitor cells.
我们研究了特发性骨髓纤维化（IMF）、真性红细胞增多症（PV）和原发性血小板增多症（ET）患者循环受限造血祖细胞的培养行为。我们发现循环中的粒细胞-巨噬细胞、红系和巨核系祖细胞存在差异，这些差异似乎是这些慢性骨髓增殖性疾病所特有的。在IMF中，受影响最大的是粒细胞-巨噬细胞祖细胞（CFU-C），其循环数量增加，并且对植物血凝素（PHA）刺激的T淋巴细胞条件培养基（CM）中存在的调节因子的敏感性存在异质性。大多数CFU-C对刺激因子要么高度敏感，要么不依赖于刺激因子，而其他CFU-C则表现出正常的敏感性。在一些IMF患者中，存在循环巨核系祖细胞（CFU-M），它们在不添加CM或促红细胞生成素（EPO）的情况下能够形成集落。在PV中，我们证实了存在循环红系祖细胞，它们在不添加EPO的情况下能够在培养中形成集落。循环CFU-C的数量正常，并且它们对CM的反应正常。在ET中，未能检测到7天循环受限祖细胞是常见的观察结果；其他循环受限祖细胞的水平处于低正常范围。因此，尽管存在某些共同特征，包括多能造血干细胞水平的原发性病变，但骨髓增殖性疾病在其循环受限祖细胞的培养行为方面存在差异。这些结果使我们推测在多能干细胞中存在第二种调节性病变，这种病变在这些疾病中有所不同，并在各自受限祖细胞水平上表现出来。
