Thiele J, Windecker R, Kvasnicka H M, Titius B R, Zankovich R, Fischer R
Institute of Pathology, University of Cologne, Germany.
Am J Hematol. 1994 May;46(1):36-42. doi: 10.1002/ajh.2830460107.
In 64 patients with primary (idiopathic) osteomyelofibrosis (OMF), a morphometric analysis has been performed on bone marrow trephine biopsies following sequential double-immunostaining with monoclonal antibodies against proliferating cell nuclear antigen (PCNA) and erythroid precursor cells (glycophorin C). The purpose of this study was to quantify erythropoiesis and its PCNA-staining capacity and, further, to determine the impact of these parameters for the development of anemia and for prognosis. In comparison with a control group (15 patients), a significant reduction in the number of erythro-normoblasts could be demonstrated, associated with an increase in PCNA-labelling. Moreover, significant correlations between the amount of nucleated erythroid marrow cells and degree of anemia (hemoglobin level, hematocrit, erythrocyte count) and survival could be calculated. Adverse relationships were assessed between number of erythroid cells, thrombocyte count, and spleen size, and also argyrophilic (reticulin/collagen) fiber density. These interactions were thought to reflect the biological behaviour of the disease process, i.e., the progression or extent of myeloid metaplasia. Our findings support ferrokinetic studies suggesting erythroid hypoplasia as one of the major causes of anemia in OMF. The remarkable high PCNA-labelling index of the macrocytic-megaloblastoid appearing erythropoiesis is probably caused by an overexpression of this marker protein. A comparative evaluation of Ki-67 antigen immunostaining in splenic tissue (myeloid metaplasia) and of the PCNA-labelling in pernicious anemia lend support to the assumption of an undue prolongation of the S-phase generated by secondary folate (hematinic) deficiency.
对64例原发性（特发性）骨髓纤维化（OMF）患者，在用抗增殖细胞核抗原（PCNA）和红系前体细胞（血型糖蛋白C）的单克隆抗体进行连续双重免疫染色后，对骨髓环钻活检标本进行了形态计量分析。本研究的目的是量化红细胞生成及其PCNA染色能力，并进一步确定这些参数对贫血发展和预后的影响。与对照组（15例患者）相比，可证明正成红细胞数量显著减少，同时PCNA标记增加。此外，可计算有核红系骨髓细胞数量与贫血程度（血红蛋白水平、血细胞比容、红细胞计数）及生存率之间的显著相关性。评估了红系细胞数量、血小板计数与脾脏大小以及嗜银（网状纤维/胶原）纤维密度之间的不利关系。这些相互作用被认为反映了疾病过程的生物学行为，即髓外化生的进展或程度。我们的研究结果支持铁动力学研究，提示红系造血低下是OMF贫血的主要原因之一。出现的巨幼样大红细胞生成的显著高PCNA标记指数可能是由该标记蛋白的过度表达引起的。对脾组织（髓外化生）中Ki-67抗原免疫染色和恶性贫血中PCNA标记的比较评估支持了继发性叶酸（补血药）缺乏导致S期过度延长的假设。
