HEMATOPOIETIC TURNOVER INDEX IN REACTIVE AND NEOPLASTIC BONE-MARROW LESIONS - QUANTIFICATION BY APOPTOSIS AND PCNA LABELING

In order to determine the dynamics of hematopoietic cell turnover, pro liferative activity and incidence of apoptosis (programmed cell death) were evaluated in bone marrow trephine biopsies. Selection of patient s (20 in each group) included in addition to a control group, idiopath ic thrombocytopenia (ITP), reactive thrombocytosis (TH), secondary pol ycythemia-smokers' polyglobuly (PG), primary (essential-hemorrhagic) t hrombocythemia (PTH), polycythemia vera (PV), and finally acute myeloi d leukemia (AML). Apoptosis was demonstrated by the in situ end-labeli ng technique (ISEL) and proliferative activity by applying the monoclo nal antibody PC10 raised against proliferating cell nuclear antigen (P CNA). To assess dynamic features of hematopoiesis, an index was calcul ated consisting of the ratio between PCNA-positive nuclei and the apop totic cell fraction. This factor was termed the hematopoietic turnover index (HTI). Morphometric analysis revealed that the HTI was signific antly increased in AML and PV. According to cell culture studies both disorders are characterized by either a prevalent proliferation of the myeloid or erythroid cell mass. On the other hand, PG, PTH, and TH sh owed no relevant enhancement of this index in comparison to the contro l specimen. In vitro experiment results are in keeping with the findin g that PG and PTH are not associated with a significant expansion of t he erythroid lineage (CFU-E). Similar to ITP and TH, in PTH megakaryoc yte proliferation (CPU-MEG) is the predominant feature of cell turnove r. Differences between PTH and TH are in line with the reduced in vitr o formation of CFU-MEG in the latter disorder. In conclusion, our in s itu study on turnover rates of the bone marrow in various neoplastic a nd reactive lesions extends previous experimental data on hematopoieti c cell kinetics.