APOPTOTIC MEGAKARYOCYTE DYSPLASIA IN THE MYELODYSPLASTIC SYNDROMES

The terminal phase of the megakaryocyte life span is characterized by the onset of apoptosis to form compact, denuded megakaryocyte nuclei (DMK) surrounded by a thin rim of cytoplasm. Increased numbers of DMK have been reported in patients with acquired immune deficiency syndrome (AIDS) and chronic myeloproliferative disorders. In this study the bone marrow biopsies of 20 patients with various FAB subtypes of myelodysplastic syndrome (MDS) were examined for the presence of DMK cells and semiquantified for marrow reticulin level. For all MDS subtypes, a 9% or greater incidence of DMK in the total megakaryocyte population of the bone marrow was associated with a significant deposit of reticulin in the marrow. Immunocytochemical staining for Factor VIII (Von Willebrand factor), showed the abnormal deposition of this megakaryocyte protein in the extravascular stroma around many of the DMK cells. These findings are consistent with a hypothesis for excess stromal reticulin based on the defective maturation and intramedullary death of large numbers of megakaryocytes. The number of DMK in the marrow biopsies of MDS patients may have prognostic significance.