Villeval J L, Metcalf D, Johnson G R
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Leukemia. 1992 Feb;6(2):107-15.
C57BL/6J murine bone marrow cells, infected with a retroviral vector (MP Zen) carrying a monkey erythropoietin cDNA, were transplanted into lethally irradiated syngeneic recipients to study the effect of erythropoietin production by hemopoietic cells. High levels of erythropoietin were recorded in the plasma (median value: 1.2 u/ml) and in media conditioned by peritoneal, spleen, and bone marrow cells from recipient mice. In transplanted mice, the hematocrit was elevated (90 +/- 5%) and the mice died at a mean of 71 days after transplantation. In the blood, platelet counts were usually low and nucleated blood cells slightly elevated. Spleen weight increased 5-fold and bone marrow cellularity decreased slightly. There was a 9.9-fold increase in erythroblast numbers, a 2-fold reduction of lymphocytes, and no variation of the myeloid cells when the total cellularity of bone marrow, spleen, peripheral blood, and peritoneal cells were considered. Calculation of the total numbers of progenitor cells in these organs revealed a 18-fold increase in erythroid colony-forming units (CFU-E) but no significant variation of the erythroid burst-forming units (BFU-E), and myeloid progenitor cell numbers. A variable proportion of CFU-E, (12% or 24% in bone marrow or spleen, respectively) was able to proliferate in unstimulated cultures. Erythropoietic amplification occurred in the spleen and there was a redistribution of the BFU-E and myeloid cells from the bone marrow to the spleen. No significant extramedullary erythropoiesis was seen. This study emphasizes the erythroid specificity of erythropoietin and shows that elevated dysregulated erythropoietin production by hemopoietic cells leads to a fatal polycythemia without erythroid neoplastic transformation.
将携带猴促红细胞生成素cDNA的逆转录病毒载体（MP Zen）感染的C57BL/6J小鼠骨髓细胞，移植到经致死剂量照射的同基因受体小鼠体内，以研究造血细胞产生促红细胞生成素的作用。在血浆（中位数：1.2 u/ml）以及受体小鼠的腹膜、脾脏和骨髓细胞条件培养基中均检测到高水平的促红细胞生成素。移植后的小鼠，血细胞比容升高（90±5%），平均在移植后71天死亡。血液中血小板计数通常较低，有核血细胞略有升高。脾脏重量增加了5倍，骨髓细胞数量略有减少。当考虑骨髓、脾脏、外周血和腹膜细胞的总细胞数时，幼红细胞数量增加了9.9倍，淋巴细胞减少了2倍，髓样细胞数量无变化。对这些器官中祖细胞总数的计算显示，红系集落形成单位（CFU-E）增加了18倍，但红系爆式集落形成单位（BFU-E）和髓样祖细胞数量无显著变化。可变比例的CFU-E（分别在骨髓或脾脏中为12%或24%）能够在未刺激的培养物中增殖。脾脏中发生了红细胞生成扩增，并且BFU-E和髓样细胞从骨髓重新分布到脾脏。未观察到明显的髓外红细胞生成。本研究强调了促红细胞生成素的红系特异性，并表明造血细胞产生的失调促红细胞生成素升高会导致致命的红细胞增多症，而无红系肿瘤转化。
