PROLIFERATING CELL NUCLEAR ANTIGEN (PCNA) EXPRESSION OF MEGAKARYOCYTOPOIESIS IN NORMAL HUMAN BONE-MARROW AND REACTIVE LESIONS WITH SPECIAL EMPHASIS ON HIV-MYELOPATHY

A morphometric analysis was performed on bone marrow trephine biopsies using sequential double-immunostaining, to evaluate endoreduplicative activity of megakaryocytopoiesis. A total of 104 marrow specimens wer e studied with employment of monoclonal antibodies PC10 (anti-prolifer ating cell nuclear antigen - PCNA) and Y2/51-CD61 (anti-platelet glyco protein IIIa). In addition to the control group patients included non- specific inflammatory changes, HIV-myelopathy with normal or decreased platelet counts, idiopathic thrombocytopenic purpura (ITP), and final ly reactive thrombocytosis (TH). To exclude an undue overexpression of PCNA, in a comparative pilot study we also applied MIB1 (Ki-67 antige n) on normal bone marrow specimens. In accordance with the various mod alities of cell-cycle marker expression, no significantly different fi ndings were disclosed. PCNA-labelling index was relatively low, rangin g from 0.8 to 1.7% of the total megakaryocytopoiesis (promegakaryoblas ts to mature platelet-shedding megakaryocytes). A significant relation ship between megakaryocyte size and PCNA-expression was determinable. This implies that some of the cases with a prevalence of small megakar yocytes, like ITP, have the tendency to show a higher proportion of po sitively-stained cells. Moreover, this feature confirms a hypothesis p ostulating a decrease in the time for DNA-synthesis (S-phase) and a re lative prolongation of the G1/G2-phases of the cell-cycle at higher pl oidy levels (large-sized megakaryocytes). On the other hand, it may be speculated that some of the hyperpolyploid giant megakaryocytes may h ave reached their endstage of endoreduplication and enter into G0-phas e. In comparison with the control group and the other entities under s tudy, a significant reduction of PCNA-reactivity was recognizable in H IV-myelopathy accompanied by thrombocytopenia. Our findings are in kee ping with cell culture studies assuming that, opposed to ITP and TH, i n AIDS different kinetic properties of the megakaryocytic lineage have to be encountered. In this context, it may not entirely be ruled out that viral infection has an inhibitory effect on the stability of mRNA for PCNA and therefore could cause an undue reduction of PCNA-immunos taining.