Apoptosis (programmed cell death) in idiopathic (primary) osteo-/myelofibrosis: naked nuclei in megakaryopoiesis reveal features of para-apoptosis.

Abstract

There is general agreement that apoptosis (programmed/physiological cell death) plays an important role in regulating normal hematopoiesis and that so-called naked nuclei (NN) present end stages of megakaryopoiesis. Using in situ end-labeling techniques (ISEL), a morphometric analysis was performed on bone marrow trephine biopsies repeatedly derived from patients with idiopathic (primary) osteo-/myelofibrosis (IMF). The purpose of this study was to quantify apoptosis and to elucidate its relationship with NN of megakaryopoiesis. Moreover, evolution of this phenomenon during progression of myelofibrosis (assessed by morphometry of silver-stained sequential biopsies) and its predictive value were investigated. In IMF, morphometric measurements revealed a rate of ISEL-positive cells that was significantly higher than previously published data on the normal bone marrow and in patients with acute myeloblastic leukemia, but lower than in the myelodysplastic syndromes. However, NN with their tightly packed (nuclear) lobules and condensed chromatin were not reactive. Statistical evaluation failed to show a significant correlation between incidence of apoptotic cells and fiber density or an increase in this feature associated with progression of fibro-osteosclerotic marrow changes and prognosis. The failure of NN to react in ISEL implicates an absence of DNA fragmentation characteristic of apoptosis. For this reason our findings are in keeping with the assumption that NN are compatible with para-apoptosis.