Erythropoiesis in primary (idiopathic) osteomyelofibrosis: quantification, PCNA-reactivity, and prognostic impact

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.